{ "papers": { "40522761": { "pmid": "40522761", "title": "Potential common pathogenesis of several neurodegenerative diseases.", "abstract": "With the gradual advancement of research methods and technologies, various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases. However, current descriptions of these biological processes do not fully explain the onset, progression, and development of these conditions. Therefore, exploration of the pathogenesis of neurodegenerative diseases remains a valuable area of research. This review summarizes the potential common pathogeneses of Alz", "journal": "Neural regeneration research", "date": "2026 Mar", "authors": "Fan T, Peng J, Liang H, Chen W, Wang J et al. (6 authors)", "query": "huntington disease treatment", "discovered": "2026-03-28T10:55:59.125892", "analysis": { "category": "review", "targets": [], "compounds": [], "finding": "Research findings have indicated that several common biological processes contribute to the pathogenesis of neurodegenerative diseases.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "40650880": { "pmid": "40650880", "title": "Brain atrophy patterns in anti-IgLON5 disease.", "abstract": "Anti-IgLON5 disease is an autoimmune encephalitis that presents with a heterogenous clinical phenotype, including sleep disorders, movement abnormalities and bulbar involvement. It is characterized by autoantibodies against IgLON5, 85% association with HLA-DQB1*05:\u223c and a brainstem-dominant tauopathy. Cellular and murine models report pathogenic effects of the autoantibodies, and neurodegenerative factors suggest progressive atrophy as a common sequela. However, evidence from in vivo patient dat", "journal": "Brain : a journal of neurology", "date": "2026 Mar", "authors": "Yogeshwar SM, Bartels F, Gr\u00fcter T, Mu\u00f1iz-Castrillo S, Picard G et al. (39 authors)", "query": "huntington disease treatment", "discovered": "2026-03-28T10:56:05.961150", "analysis": { "category": "clinical_trial", "targets": [ "IgLON5" ], "compounds": [], "finding": "Brain atrophy patterns in anti-IgLON5 disease show a brainstem-dominant tauopathy.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41813136": { "pmid": "41813136", "title": "ALS and Huntington Disease: Unraveling the Connections between TDP-43 and Huntingtin.", "abstract": "Amyotrophic lateral sclerosis (ALS) and Huntington disease (HD) are lethal neurodegenerative diseases affecting motor function. Though their etiology and pathology are distinct, recent evidence suggests commonalities between TAR DNA-binding protein (TDP-43), which is associated with 97% of ALS cases, and huntingtin (HTT), the causative protein of HD. ALS is a heterogeneous, lethal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons, as well as brainst", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "date": "2026 Mar", "authors": "Perry CM, Martin DDO", "query": "huntington disease treatment", "discovered": "2026-03-28T10:56:13.828424", "analysis": { "category": "mechanism", "targets": [ "TDP-43", "huntingtin (HTT)" ], "compounds": [], "finding": "Recent evidence suggests commonalities between TDP-43 and huntingtin in the pathology of ALS and HD.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The study highlights a potential link between two distinct neurodegenerative diseases, suggesting a shared molecular mechanism." } }, "40576748": { "pmid": "40576748", "title": "Innovative Interventions: Postbiotics and Psychobiotics in Neurodegenerative Disease Treatment.", "abstract": "Neurodegenerative disorders, including Huntington's disease, Amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease, create more challenges as the population gets older and there are no curative therapies available. Recent advances in gut microbiome research have spotlighted postbiotics and psychobiotics as innovative therapeutic strategies targeting the gut-brain axis to alleviate neurodegenerative symptoms and slow disease progression. Postbiotics, which are metabolites an", "journal": "Probiotics and antimicrobial proteins", "date": "2026 Mar", "authors": "Gupta MK, Chauhan K, Bhardwaj S, Srivastava R", "query": "huntington disease treatment", "discovered": "2026-03-28T10:56:20.732593", "analysis": { "category": "review", "targets": [], "compounds": [ "postbiotics", "psychobiotics" ], "finding": "Postbiotics and psychobiotics may offer novel approaches to neuroprotection in neurodegenerative diseases.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41295902": { "pmid": "41295902", "title": "Huntington's disease clinical trials update: October 2025.", "abstract": "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the launch of the phase II/III clinical trial of SKY-0515 from Skyhawk Therapeutics and the phase I/II clinical trial of SPK-10001 from Spark Therapeutics. We also report positive topline data from uniQure's phase I/II clinical trial of AMT-130 after 36 months of follow-up. Further updates include recent developments in Roche's tominersen programme within GENERATION HD2, progress with votoplam (PTC518) in PIVOT-HD b", "journal": "Journal of Huntington's disease", "date": "2026 Feb", "authors": "Farag M, Tabrizi SJ, Wild EJ", "query": "huntington disease treatment", "discovered": "2026-03-28T10:56:29.091326", "analysis": { "category": "clinical_trial", "targets": [], "compounds": [ "SKY-0515", "SPK-10001", "AMT-130", "tominersen", "votoplam (PTC518)", "pridopidine" ], "finding": "Several clinical trials for Huntington's disease show promising results, including positive topline data from uniQure's phase I/II trial of AMT-130.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41841355": { "pmid": "41841355", "title": "Discovery and Optimization of Thienopyrazine RNA-Splicing Modulators for the Treatment of Huntington's Disease.", "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG-repeat expansion in the Huntington gene (HTT). Herein, we describe the discovery of a series of HTT pre-mRNA-splicing modulators that promote the inclusion of a cryptic stop codon that in turn lowers levels of mutant Huntington protein (mHTT). Optimization of the starting thienopyridine amide core resulted in the discovery of the potent, CNS-penetrant, selective, and orally bioavailable HTT-splicing modulator B", "journal": "Journal of medicinal chemistry", "date": "2026 Mar", "authors": "Xu C, Abraham N, Bansal N, Bolduc PN, Cullen P et al. (31 authors)", "query": "huntington disease treatment", "discovered": "2026-03-28T10:56:37.966116", "analysis": { "category": "small_molecule", "targets": [ "HTT (Huntington gene)" ], "compounds": [ "BIO-6553", "thienopyridine amide core" ], "finding": "Discovery of a potent, CNS-penetrant HTT-splicing modulator that lowers levels of mutant Huntington protein.", "relevance": "high", "repurposing_potential": false, "novel_insight": "Optimization of the thienopyridine amide core led to the discovery of a structurally distinct and orally bioavailable HTT-splicing modulator." } }, "41318997": { "pmid": "41318997", "title": "The impact of tau deletion on Huntington's disease: An in vivo perspective.", "abstract": "Although an emerging body of evidence suggests that abnormal forms of tau are present and contribute to Huntington's disease (HD)-a genetic neurodegenerative disorder primarily characterized by the aggregation of the mutant huntingtin (mHtt) protein affecting cognitive, motor, and psychiatric function-it is not clear to what extent this is relevant to the disease phenotype, and hence future treatments. We therefore generated a novel murine model by crossing heterozygous zQ175 knockin HD mice wit", "journal": "Molecular therapy : the journal of the American Society of Gene Therapy", "date": "2026 Mar", "authors": "Lepinay E, Saint-Pierre M, Teixeira M, Snapyan M, Oueslati A et al. (8 authors)", "query": "huntington disease treatment", "discovered": "2026-03-28T10:56:44.834606", "analysis": { "category": "mechanism", "targets": [ "tau", "mHtt" ], "compounds": [], "finding": "Tau deletion exacerbated both motor and cognitive deficits in HD mice.", "relevance": "high", "repurposing_potential": false, "novel_insight": "Tau's role in HD is more significant than previously thought." } }, "41846052": { "pmid": "41846052", "title": "Human iPSC-derived exosomes for amelioration of Huntington's disease through mitochondrial, synaptic, and anti-apoptotic mechanisms.", "abstract": "Huntington's disease (HD) is driven by expanded CAG repeats in the huntingtin gene, resulting in mutant huntingtin (mHtt) aggregation, mitochondrial dysfunction, neuronal loss, and neuroinflammation. Although stem cell-based therapies provide potent regenerative, anti-inflammatory, and neuroprotective effects, their clinical translation remains constrained by tumorigenicity and poor engraftment efficiency. Therefore, we investigated whether exosomes derived from human induced pluripotent stem ce", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "date": "2026 Apr", "authors": "Jahng S, Palomar-Alonso N, Moon J, Yang BG, Lee M et al. (6 authors)", "query": "huntington disease treatment", "discovered": "2026-03-28T10:56:52.988440", "analysis": { "category": "gene_therapy", "targets": [ "huntingtin gene", "mutant huntingtin (mHtt)" ], "compounds": [], "finding": "Human iPSC-derived exosomes show potential for ameliorating Huntington's disease through mitochondrial, synaptic, and anti-apoptotic mechanisms.", "relevance": "high", "repurposing_potential": false, "novel_insight": "Exosomes derived from human induced pluripotent stem cells can serve as a safe, cell-free therapeutic approach for HD." } }, "41238102": { "pmid": "41238102", "title": "Targeting lipid metabolism in neurodegenerative diseases: From experimental to clinical.", "abstract": "The human brain, despite accounting for only 2\u00a0% of total body weight, exhibits an exceptionally high lipid content (approximately 20\u00a0% of its mass), highlighting the critical role of lipid metabolism in maintaining neural homeostasis and function. Neurodegenerative diseases-including Alzheimer's disease (AD), Parkinson's disease (PD), stroke, Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS)-are characterized by progressive neuronal dysfunction and myelin degeneration. These co", "journal": "Metabolism: clinical and experimental", "date": "2026 Feb", "authors": "Long J, Liu S, Shi Y, Zhang C, Qin L et al. (6 authors)", "query": "huntington disease treatment", "discovered": "2026-03-28T10:56:59.264909", "analysis": { "category": "mechanism", "targets": [ "lipid metabolism" ], "compounds": [], "finding": "Dysregulated lipid metabolism is involved in the pathogenesis of neurodegenerative diseases.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41721094": { "pmid": "41721094", "title": "Gene therapy for huntington's disease: advances, challenges, and future perspectives.", "abstract": "", "journal": "Neurogenetics", "date": "2026 Feb", "authors": "Kaushal R, Yadav M, Kosey S, Dwivedi M", "query": "huntington disease gene therapy", "discovered": "2026-03-28T10:57:08.967289", "analysis": { "category": "gene_therapy", "targets": [ "HTT gene" ], "compounds": [], "finding": "Gene therapy approaches show promise in reducing mutant huntingtin protein levels and alleviating disease symptoms.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41827217": { "pmid": "41827217", "title": "The New Wave of Gene and Cell Therapies Across Diseases.", "abstract": "Recent years have seen rapid progress in biological treatments for genetic diseases, as well as conditions like type 1 diabetes that lack an obvious genetic component. The authors sought to explain why this progress has emerged at this particular moment. The best way to illustrate this is by showcasing a wide range of therapies targeting diverse diseases. This progress has been driven by technological advances in genetically modified CAR-T and CAR-NK cells (e.g., using CRISPR or transgenes), whi", "journal": "Journal of clinical medicine", "date": "2026 Feb", "authors": "Rieske A, Grot D, Tr\u0119da C, W\u0142odarczyk A, Stoczy\u0144ska-Fidelus E et al. (7 authors)", "query": "huntington disease gene therapy", "discovered": "2026-03-28T10:57:15.221969", "analysis": { "category": "gene_therapy", "targets": [ "Huntington's disease" ], "compounds": [], "finding": "Recent years have seen rapid progress in biological treatments for genetic diseases.", "relevance": "medium", "repurposing_potential": false, "novel_insight": null } }, "41783572": { "pmid": "41783572", "title": "Copper Homeostasis and Cuproptosis in Neurological Disorders.", "abstract": "Neurological disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) pose a serious global public health threat, with complex etiologies involving genetic, environmental, and metabolic factors. Current data indicate that the prevalence of these disorders is rapidly increasing with the aging population, resulting in a growing economic and healthcare burden worldwide. In recent years, the imbalance of copper homeostasis has been increasingly implicated in the pathogenesis of neurol", "journal": "Drug design, development and therapy", "date": "2026", "authors": "Liu W, Xue Y, Cao C, Yang L, Zhang L", "query": "huntington disease gene therapy", "discovered": "2026-03-28T10:57:21.981179", "analysis": { "category": "mechanism", "targets": [ "copper homeostasis" ], "compounds": [], "finding": "Copper imbalance contributes to the pathogenesis of neurological diseases by inducing oxidative stress and mitochondrial dysfunction.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "40421472": { "pmid": "40421472", "title": "Use of antidepressants in early Huntington's Disease: a systematic review and meta-analysis.", "abstract": "While neuropsychiatric symptoms are common in Huntington's Disease (HD), there is a dearth of evidence about the effectiveness of psychotropic medication for treating behavioral and cognitive symptoms. This article systematically reviews and aggregates the evidence of the effects of antidepressants on individuals with early HD. A systematic review and random-effects meta-analysis of RCTs comparing antidepressants to placebo in individuals with HD was performed, with a focus on outcomes of execut", "journal": "Neurodegenerative disease management", "date": "2026 Feb", "authors": "Tiwari V, Dutta S, Alkharboush F, Velit MR, Espinel Z", "query": "huntington disease gene therapy", "discovered": "2026-03-28T10:57:28.419586", "analysis": { "category": "review", "targets": [], "compounds": [ "antidepressants" ], "finding": "A modest but statistically significant improvement in symptoms was observed with antidepressant use in early Huntington's Disease.", "relevance": "high", "repurposing_potential": true, "novel_insight": null } }, "41690900": { "pmid": "41690900", "title": "Huntington's disease is the best investment in neuroscience today.", "abstract": "Huntington's disease (HD) is usually described as rare, tragic, and intractable. Yet, HD offers a strategically unique entry point for neuroscience. With its genetic clarity, relatively predictable course, and organized global community, HD provides the clearest path to advancing brain repair.", "journal": "Trends in molecular medicine", "date": "2026 Mar", "authors": "Maimon R", "query": "huntington disease gene therapy", "discovered": "2026-03-28T10:57:35.048525", "analysis": { "category": "mechanism", "targets": [ "Huntington's disease" ], "compounds": [], "finding": "HD offers a strategically unique entry point for neuroscience due to its genetic clarity and relatively predictable course.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41663779": { "pmid": "41663779", "title": "Tailoring treatments: pharmacogenomics in the management of neurodegenerative diseases.", "abstract": "Neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis are growing more common worldwide, yet treatment is still poor. Conventional therapies can have unforeseen side effects, produce poor medication reactions, and take longer to work. This persistent treatment gap highlights the need for novel approaches to these disorders' complex distinctions. Pharmacogenomics, which examines how genetic differences affect drug response, is a promising new su", "journal": "Acta neurologica Belgica", "date": "2026 Feb", "authors": "Roy KK, Kumari R, Upadhyay AK, Mohanty S", "query": "huntington disease gene therapy", "discovered": "2026-03-28T10:57:41.090381", "analysis": { "category": "review", "targets": [], "compounds": [], "finding": "Pharmacogenomics tailors medicine selection and administration to each patient's genetic profile.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41376158": { "pmid": "41376158", "title": "Administration of a barcoded AAV capsid library to the putamen of non-human primates identifies variants with efficient retrograde transport.", "abstract": "Adeno-associated viral vectors have become a leading choice for gene therapy in the central nervous system due to their safety profile, efficient neuronal transduction, and capacity for sustained transgene expression. We previously reported that AAV2-derived capsids developed using the BRAVE (Barcoded Rational AAV Vector Evolution) approach have enhanced retrograde transport properties in the rodent brain, compared with parental AAV2. Retrograde transport enables broader coverage of connected br", "journal": "Molecular therapy : the journal of the American Society of Gene Therapy", "date": "2026 Mar", "authors": "Dzhashiashvili Y, McBride JL, Fabyanic E, Huang X, Kelly BM et al. (16 authors)", "query": "huntington disease gene therapy", "discovered": "2026-03-28T10:57:49.959925", "analysis": { "category": "gene_therapy", "targets": [ "Huntington's disease" ], "compounds": [ "AAV capsid library", "barcoded AAV vectors" ], "finding": "A barcoded AAV capsid library was used to identify variants with efficient retrograde transport in non-human primates.", "relevance": "high", "repurposing_potential": false, "novel_insight": "Efficient retrograde transport of AAV vectors can be achieved using a barcoded AAV capsid library, which may improve gene therapy outcomes for Huntington's disease and other neurodegenerative disorders." } }, "41770933": { "pmid": "41770933", "title": "Huntington's disease LIG1 modifier variant increases ligase fidelity and suppresses somatic CAG repeat expansion.", "abstract": "Huntington's disease (HD) is a fatal neurodegenerative disorder caused by inheriting an expanded CAG repeat tract in the huntingtin gene (", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "date": "2026 Mar", "authors": "Lee E, Kim W, Beier DH, Lee Y, Kovalenko M et al. (23 authors)", "query": "huntington somatic expansion CAG", "discovered": "2026-03-28T10:58:00.267562", "analysis": { "category": "mechanism", "targets": [ "LIG1", "huntingtin gene" ], "compounds": [], "finding": "A modifier variant in the LIG1 gene increases ligase fidelity and suppresses somatic CAG repeat expansion.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The study reveals a new mechanism by which a genetic variant can influence the progression of Huntington's disease." } }, "41622913": { "pmid": "41622913", "title": "The HTT1a protein initiates HTT aggregation in a knock-in mouse model of Huntington's disease.", "abstract": "The mutation that causes Huntington's disease is a CAG repeat expansion in exon 1 of the huntingtin gene (HTT) that leads to an abnormally long polyglutamine tract in the huntingtin protein (HTT). Mutant CAG repeats are unstable and increase in size in specific neurons and brain regions with age, a phenomenon that constitutes the first step in the pathogenesis of the disease. In the presence of an expanded CAG repeat, cryptic polyA sites in intron 1 of the HTT pre-mRNA can become activated leadi", "journal": "Brain : a journal of neurology", "date": "2026 Feb", "authors": "Papadopoulou AS, Landles C, Smith EJ, Bondulich MK, Boeddrich A et al. (19 authors)", "query": "huntington somatic expansion CAG", "discovered": "2026-03-28T10:58:08.514622", "analysis": { "category": "mechanism", "targets": [ "HTT", "HTT1a" ], "compounds": [], "finding": "The production of HTT1a protein may be the mechanism through which expanded CAG repeats lead to Huntington's disease.", "relevance": "high", "repurposing_potential": false, "novel_insight": "HTT1a is a highly aggregation-prone and pathogenic protein generated from cryptic polyA sites in intron 1 of the HTT pre-mRNA." } }, "41755664": { "pmid": "41755664", "title": "Contribution of neuroepigenetics to HD - developmental and aging-related signatures.", "abstract": "Huntington's disease (HD) is a neurodegenerative disorder triggered by an unstable expansion of CAG repeats in the coding sequence of the ", "journal": "Journal of Huntington's disease", "date": "2026 Feb", "authors": "Scuto J, Penaud N, Merienne K", "query": "huntington somatic expansion CAG", "discovered": "2026-03-28T10:58:14.797860", "analysis": { "category": "mechanism", "targets": [ "CAG repeats" ], "compounds": [], "finding": "Huntington's disease is triggered by an unstable expansion of CAG repeats in the coding sequence of the gene.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41841481": { "pmid": "41841481", "title": "Challenges facing genetic diagnostics of Huntington's disease: an update.", "abstract": "Since 1993, when a polymorphic CAG trinucleotide repeat was established as the cause of Huntington's disease (HD), fragment analysis has been the first-tier test in genetic diagnosis of HD. However, in recent years it has become increasingly clear that, in addition to the repeat length itself, sequence variations within the Sequence interruptions or non-canonical repeat motifs have historically been difficult to identify, as PCR cannot distinguish an interrupted repeat tract when assessed by ca", "journal": "Expert review of molecular diagnostics", "date": "2026 Mar", "authors": "Arning L, Saft C, Nguyen HP", "query": "huntington somatic expansion CAG", "discovered": "2026-03-28T10:58:21.139669", "analysis": { "category": "review", "targets": [ "Huntington's disease gene (HD)" ], "compounds": [], "finding": "Current genetic diagnostic methods for Huntington's disease may underestimate repeat length due to sequence variations.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41849583": { "pmid": "41849583", "title": "Lowering the ", "abstract": "Lowering ", "journal": "Science translational medicine", "date": "2026 Mar", "authors": "Papadopoulou AS, Alterman J, Landles C, Smith EJ, Conroy F et al. (21 authors)", "query": "huntington somatic expansion CAG", "discovered": "2026-03-28T10:58:27.314920", "analysis": { "category": "gene_therapy", "targets": [ "HTT gene" ], "compounds": [], "finding": "Reduced mutant huntingtin protein levels in patient-derived cells.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41849580": { "pmid": "41849580", "title": "Selective targeting of mutant ", "abstract": "Huntington's disease (HD) arises from the toxic gain of function caused by a CAG expansion in the coding region of the ", "journal": "Science translational medicine", "date": "2026 Mar", "authors": "Bragg RM, Landles C, Smith EJ, Osborne GF, Mathews EW et al. (8 authors)", "query": "huntington somatic expansion CAG", "discovered": "2026-03-28T10:58:34.122072", "analysis": { "category": "mechanism", "targets": [ "Huntington's disease (HD)" ], "compounds": [], "finding": "Huntington's disease arises from the toxic gain of function caused by a CAG expansion in the coding region of the gene.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41738896": { "pmid": "41738896", "title": "Zebrafish as a Versatile Screening Model for Neurological Diseases: Insights Into Biology, Drug Delivery and Therapeutic Discovery.", "abstract": "Neurological diseases such as Alzheimer's disease, Parkinson's disease, anxiety, depression, and Huntington's disease pose significant challenges due to their complex pathophysiology and limited treatment options. Traditional mammalian models, although widely used, often face limitations in cost, ethical concerns, and scalability. Zebrafish have become an excellent animal model for neurological research in recent years because of their remarkable genetic similarity to humans, well-preserved neur", "journal": "Journal of biochemical and molecular toxicology", "date": "2026 Mar", "authors": "Vyavahare S, Pawar A, Sayyed SA, Shegar N, Raykar S et al. (7 authors)", "query": "huntington drug repurposing", "discovered": "2026-03-28T10:58:43.741216", "analysis": { "category": "review", "targets": [], "compounds": [], "finding": "Zebrafish can be used as a versatile screening model for neurological diseases due to their genetic similarity to humans and well-preserved neurotransmitter systems.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41879495": { "pmid": "41879495", "title": "Emerging Roles of Small-molecule Derivatives in Modulating Neurodegenerative Pathways: From Molecular Targets to Therapeutic Applications.", "abstract": "Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease involve progressive neuronal dysfunction driven by mechanisms including protein aggregation, oxidative stress, mitochondrial impairment, and neuroinflammation. Current treatments are largely symptomatic, with limited disease-modifying options. Advances in medicinal chemistry have led to the development of small-molecule derivatives targeting specific pathological ", "journal": "Mini reviews in medicinal chemistry", "date": "2026 Mar", "authors": "Singh K, Sethi P, Jain D, Gupta JK, Alsaidan OA et al. (9 authors)", "query": "huntington drug repurposing", "discovered": "2026-03-28T10:58:51.716332", "analysis": { "category": "review", "targets": [ "amyloid-\u03b2 metabolism", "tau acetylation", "\u03b1-synuclein aggregation", "RNA-binding protein interactions", "NLRP3 inflammasome activation" ], "compounds": [ "small-molecule derivatives" ], "finding": "Recent progress in medicinal chemistry has led to the development of small-molecule derivatives targeting specific pathological pathways.", "relevance": "high", "repurposing_potential": true, "novel_insight": null } }, "41639620": { "pmid": "41639620", "title": "Design and evaluation of semantically-valid negative samples integration techniques for scalable semi-automated drug repurposing prediction pipelines in rare disease research.", "abstract": "Computational approaches involving complex data structures (e.g. machine learning, knowledge graphs) have been more prominent in biological studies for the last two decades. Due to increasingly larger amounts of data collected with modern omics techniques, there is a need for methods that can process such data quickly and thoroughly. In addition, those techniques can be applied to extrapolate results from a limited number of observations. Rare disease research benefits particularly from those ne", "journal": "BMC bioinformatics", "date": "2026 Feb", "authors": "Bianchi N, Lefebvre AEJL, Wolstencroft KJ, Spruit M", "query": "huntington drug repurposing", "discovered": "2026-03-28T10:58:58.258966", "analysis": { "category": "ai_ml", "targets": [], "compounds": [], "finding": "Computational approaches can be applied to rare disease research for scalable semi-automated drug repurposing prediction pipelines.", "relevance": "high", "repurposing_potential": true, "novel_insight": null } }, "41492395": { "pmid": "41492395", "title": "Neural and biomarker correlates of the Parkinson's Disease-Cognitive Rating Scale in Huntington's disease.", "abstract": "Cognitive decline is a core feature of Huntington's disease (HD), often preceding motor symptoms and progressing with disease severity. While several neuropsychological tests track cognitive changes, few studies have examined the biological correlates of brief screening tools adapted for HD. This study investigates the neuroanatomical and fluid biomarker correlates of performance on the Parkinson's Disease-Cognitive Rating Scale (PD-CRS), aiming to validate it as a clinically and biologically gr", "journal": "Neuroimage. Reports", "date": "2026 Mar", "authors": "Martinez-Horta S, Puig-Davi A, Sampedro F, P\u00e9rez-P\u00e9rez J, Franch-Mart\u00ed C et al. (12 authors)", "query": "huntington biomarker neurofilament", "discovered": "2026-03-28T10:59:07.773249", "analysis": { "category": "biomarker", "targets": [ "neurofilament light chain (NfL)" ], "compounds": [], "finding": "Plasma neurofilament light chain levels correlate with cognitive decline in Huntington's disease.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41699789": { "pmid": "41699789", "title": "Huntington's Disease: An Overview of Biomarkers in Prognostic, Diagnostic, and Therapeutic Management.", "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and psychiatric disturbances. It is caused by the abnormal expansion of cytosine-adenine-guanine triplet repeats in the HTT gene, leading to the production of mutant huntingtin (mHTT) protein. This protein contributes to neuronal dysfunction and cell death, particularly in the striatum and cortex. The review examines recent research focused on identifying and assessing pot", "journal": "Rejuvenation research", "date": "2026 Feb", "authors": "Singh G, Singh C, Singh A", "query": "huntington biomarker neurofilament", "discovered": "2026-03-28T10:59:14.186869", "analysis": { "category": "review", "targets": [ "HTT gene" ], "compounds": [], "finding": "Neurofilament light chain and mHTT emerge as robust indicators of disease progression in Huntington's disease.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41527739": { "pmid": "41527739", "title": "Insights into phosphoproteomic studies and prospects of phosphoproteins as biomarkers for brain disorders.", "abstract": "The dysregulation of phosphorylation networks plays a critical role in the pathogenesis of a wide spectrum of brain disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, ischemic stroke, drug abuse, major depressive disorder, and schizophrenia. Notably, phosphorylated isoforms of microtubule-associated protein tau and neurofilament heavy polypeptide are already utilized in clinical diagnostics, highlighting the", "journal": "Journal of Alzheimer's disease : JAD", "date": "2026 Mar", "authors": "Le J, Hu X, Jiang Y, Wang Q, Ma Q et al. (6 authors)", "query": "huntington biomarker neurofilament", "discovered": "2026-03-28T10:59:21.206371", "analysis": { "category": "biomarker", "targets": [ "microtubule-associated protein tau", "neurofilament heavy polypeptide" ], "compounds": [], "finding": "Phosphoproteomic studies reveal potential biomarkers for brain disorders, including Huntington's disease.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41828602": { "pmid": "41828602", "title": "A Two-Track Model of Huntington's Disease Pathology: Striatal Atrophy Mediates Maladaptive Immune Dysregulation.", "abstract": "Huntington's disease (HD) is characterized by progressive striatal atrophy and complex proteomic changes in the central nervous system. Using the ultrasensitive Next-Gen Ultra-Sensitive Immunoassay (NULISA) proteomic platform, we analyzed cerebrospinal fluid (CSF) from 88 persons with HD to dissect the biological correlates of gray matter loss. Our findings reveal a distinct \"Two-Track\" model of pathology. The first track, marked by the axonal damage protein neurofilament light chain (NEFL), sho", "journal": "International journal of molecular sciences", "date": "2026 Mar", "authors": "Bockholt HJ, Clemsen JD, Baker BT, Calhoun VD, Paulsen JS", "query": "huntington biomarker neurofilament", "discovered": "2026-03-28T10:59:29.198627", "analysis": { "category": "biomarker", "targets": [ "neurofilament light chain (NEFL)" ], "compounds": [], "finding": "A distinct 'Two-Track' model of Huntington's disease pathology was identified, with axonal damage protein NEFL inversely correlated with putamen volume.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The study provides new insights into the relationship between striatal atrophy and immune dysregulation in HD." } }, "41762390": { "pmid": "41762390", "title": "Multiple System Atrophy Combined Outcome Assessment (MuSyCA): process, format, and validation plan.", "abstract": "The Unified Multiple System Atrophy Rating Scale (UMSARS) is widely used as an outcome measure in MSA trials, but it has limitations\u00a0for clinical trial use. To address these, we developed the Multiple System Atrophy Combined Outcome Assessment (MuSyCA), a comprehensive multimodal tool for disease-modifying MSA\u00a0trials. The purpose of this manuscript is to describe the development and validation plan for MuSyCA, with emphasis on its structure, intended use, and assessment of reliability, validity,", "journal": "Clinical autonomic research : official journal of the Clinical Autonomic Research Society", "date": "2026 Feb", "authors": "Kaufmann H, Palma JA, Millar Vernetti P, Kuijpers M, Nkrumah G et al. (25 authors)", "query": "huntington biomarker neurofilament", "discovered": "2026-03-28T10:59:35.631417", "analysis": { "category": "clinical_trial", "targets": [], "compounds": [], "finding": "A new outcome assessment tool, MuSyCA, was developed to track disease progression in Multiple System Atrophy trials.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41406849": { "pmid": "41406849", "title": "Molecular diagnostics in clinical microbiology: Advances, applications, and future directions.", "abstract": "Molecular diagnostics have transformed clinical microbiology by enabling rapid, accurate, and highly sensitive detection of infectious agents, significantly improving patient outcomes and public health response. Over the past decade, advances in polymerase chain reaction (PCR), next-generation sequencing (NGS), digital PCR, isothermal amplification, and CRISPR-based assays have enhanced pathogen identification, antimicrobial resistance profiling, and outbreak investigation. These technologies ha", "journal": "Diagnostic microbiology and infectious disease", "date": "2026 Mar", "authors": "Asokan S, Choudekar A, Jagadeesan A, Sm R, Ali A et al. (14 authors)", "query": "huntington CRISPR", "discovered": "2026-03-28T10:59:45.025870", "analysis": { "category": "other", "targets": [], "compounds": [], "finding": "Molecular diagnostics have transformed clinical microbiology by enabling rapid, accurate, and highly sensitive detection of infectious agents.", "relevance": "low", "repurposing_potential": false, "novel_insight": null } }, "41674784": { "pmid": "41674784", "title": "CRISPR-Cas technologies in neurodegenerative disorders: mechanistic insights, therapeutic potential, and translational challenges.", "abstract": "CRISPR-Cas genome-editing technologies have emerged as powerful tools for precise DNA and RNA modulation, offering promising therapeutic strategies for neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This review critically evaluates current CRISPR/Cas applications in neurodegeneration, with emphasis on mechanistic insights, therapeutic outcomes, and translational feasibility. Preclinical a", "journal": "Frontiers in neurology", "date": "2025", "authors": "Yashooa RK, Nabi AQ, Smail SW, Azeez SS, Nooh WA et al. (9 authors)", "query": "huntington CRISPR", "discovered": "2026-03-28T10:59:52.303765", "analysis": { "category": "review", "targets": [ "pathogenic mutations", "toxic gene expression" ], "compounds": [], "finding": "CRISPR-Cas genome-editing technologies show promise in treating neurodegenerative disorders by correcting pathogenic mutations and suppressing toxic gene expression.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41840824": { "pmid": "41840824", "title": "CRISPR Gene Editing for Nucleotide Repeat Expansion Disorders: A Systematic Review of Preclinical and Clinical Evidence.", "abstract": "Incurable hereditary diseases such as Duchenne muscular dystrophy (DMD), Huntington's disease (HD), and myotonic dystrophy type 1 (DM1) fall into the nucleotide repeat expansion disorder (NRED) category. The discovery of CRISPR-Cas genome editing has paved the way toward hopeful strategies for accurate DNA-level repair. This systematic review presents preclinical data on the efficacy, molecular effects, and limitations of CRISPR-based treatments for NREDs. As per Preferred Reporting Items for Sy", "journal": "Genetic testing and molecular biomarkers", "date": "2026 Mar", "authors": "Thalib HI, Khan S, Hanin Shaikh A, Alawi KM, Alabdrabalrasol ZH et al. (9 authors)", "query": "huntington CRISPR", "discovered": "2026-03-28T10:59:58.728107", "analysis": { "category": "review", "targets": [ "DMD", "HD", "DM1" ], "compounds": [], "finding": "CRISPR-Cas genome editing shows promise for treating nucleotide repeat expansion disorders.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41784089": { "pmid": "41784089", "title": "Novel monoclonal antibodies against the C-terminal HEAT domain of huntingtin.", "abstract": "BackgroundReliable detection of huntingtin (HTT) is essential for understanding Huntington's disease (HD) biology and for evaluating therapeutic strategies. However, high-quality monoclonal antibodies (mAbs) against the HTT C-terminal domain remain limited.ObjectiveWe sought to generate and validate novel monoclonal antibodies targeting the HTT C-terminal HEAT-containing domain to better detect HTT independently of potential effects of polyglutamine length that can impact some N-terminally targe", "journal": "Journal of Huntington's disease", "date": "2026 Mar", "authors": "Park YN, Fanti R, Sadeghi S, Chandrasekaran R, Edwards AM et al. (7 authors)", "query": "huntington CRISPR", "discovered": "2026-03-28T11:00:06.776025", "analysis": { "category": "biomarker", "targets": [ "huntingtin (HTT) C-terminal HEAT-containing domain" ], "compounds": [], "finding": "Novel monoclonal antibodies targeting the HTT C-terminal HEAT-containing domain have been generated and validated.", "relevance": "high", "repurposing_potential": false, "novel_insight": "Development of high-quality monoclonal antibodies against the HTT C-terminal domain, which can detect HTT independently of polyglutamine length." } }, "41708002": { "pmid": "41708002", "title": "The Hsp40 cochaperone DNAJC7 regulates polyglutamine aggregation and exhibits context-dependent effects on polyglycine aggregation.", "abstract": "Protein-encoding nucleotide repeat expansion diseases, including polyglutamine (polyQ) and polyglycine (polyG) diseases, are characterized by the accumulation of aggregation-prone proteins. In the polyQ diseases, including Huntington's disease and several spinocerebellar ataxias, substantial prior evidence supports a pathogenic role for mutant polyQ-expanded protein misfolding and aggregation, with molecular chaperones showing promise in suppressing disease phenotypes in cellular and animal mode", "journal": "The Journal of biological chemistry", "date": "2026 Feb", "authors": "Ramani B, Ehsani K, Kampmann M", "query": "huntington CRISPR", "discovered": "2026-03-28T11:00:14.173536", "analysis": { "category": "mechanism", "targets": [ "DNAJC7" ], "compounds": [], "finding": "The Hsp40 cochaperone DNAJC7 regulates polyglutamine aggregation and exhibits context-dependent effects on polyglycine aggregation.", "relevance": "high", "repurposing_potential": false, "novel_insight": "DNAJC7 has a regulatory effect on protein aggregation in Huntington's disease" } }, "41849610": { "pmid": "41849610", "title": "Self-inactivating AAV-CRISPR at different ages enables sustained amelioration of Huntington's disease deficits in BAC226Q mice.", "abstract": "Huntington's disease (HD) is a monogenic autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the ", "journal": "Science advances", "date": "2026 Mar", "authors": "Dai Y, Abudujielili Z, Ding Y, Huang W, Yin J et al. (9 authors)", "query": "huntington CRISPR", "discovered": "2026-03-28T11:00:22.573584", "analysis": { "category": "gene_therapy", "targets": [ "Huntington's disease (HD) gene", "CAG repeat expansion in exon 1 of the" ], "compounds": [ "AAV-CRISPR" ], "finding": "Sustained amelioration of Huntington's disease deficits was achieved using self-inactivating AAV-CRISPR at different ages in BAC226Q mice.", "relevance": "high", "repurposing_potential": false, "novel_insight": "Gene therapy approach shows promise for treating HD" } }, "41618467": { "pmid": "41618467", "title": "Emerging roles of circular RNAs and enhancer RNAs: new insights into the development and management of neurodegenerative disorders.", "abstract": "Neurodegenerative disorders involve the gradual breakdown of neurons, leading to problems with thinking, movement, and mental health. More evidence is emerging about the important roles of non-coding RNAs (ncRNAs). CircRNAs are a type of ncRNA formed through back-splicing and are widely present in the mammalian brain. They play crucial roles in brain development and mainly regulate gene expression and post-transcriptional processes by acting as molecular sponges for miRNAs and RBPs. eRNAs are an", "journal": "Biomarker research", "date": "2026 Jan", "authors": "Ziaei A, Kargar M, Shirvani-Farsani Z, MehrabMohseni M", "query": "huntington antisense oligonucleotide", "discovered": "2026-03-28T11:00:32.874120", "analysis": { "category": "mechanism", "targets": [ "circRNAs", "eRNAs" ], "compounds": [], "finding": "Abnormal levels of circRNAs and eRNAs can be found in many human diseases, including neurodegenerative conditions.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The study highlights the emerging roles of non-coding RNAs (ncRNAs) in neurodegenerative disorders." } }, "41833626": { "pmid": "41833626", "title": "Autophagy-exosome crosstalk in neurodegeneration: Mechanisms and therapeutic opportunities.", "abstract": "Neurodegenerative diseases (NDs), including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and multiple sclerosis, share a common pathogenic signature: disrupted proteostasis driven by impaired autophagy and maladaptive exosome dynamics. Under normal conditions, autophagy maintains neuronal homeostasis by clearing misfolded proteins and damaged organelles, while exosomes mediate neuroglial communication. When autophagic flux is impaired or lysosomal function is compromise", "journal": "Pharmacology & therapeutics", "date": "2026 Mar", "authors": "Sedighi S, Guan T, Michetti F, Cordani M, Barzegar Behrooz A et al. (10 authors)", "query": "huntington neuroinflammation", "discovered": "2026-03-28T11:00:43.939742", "analysis": { "category": "mechanism", "targets": [ "autophagy", "exosomes" ], "compounds": [], "finding": "Impaired autophagic flux and lysosomal dysfunction can lead to the secretion of pathogenic proteins through exosomes.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The study highlights a novel mechanism by which neurodegenerative diseases, including Huntington's, may be driven by disrupted autophagy and maladaptive exosome dynamics." } }, "41407165": { "pmid": "41407165", "title": "Nutraceutical interventions for neuroprotection: a comprehensive review.", "abstract": "Nutraceuticals, bioactive compounds derived from food sources, are emerging as promising agents for neuroprotection, particularly through their modulation of gut health. Unlike conventional single-molecule therapeutics that often target isolated pathways, nutraceuticals offer a multi-targeted approach by influencing the gut-brain axis, a bidirectional communication network linking the gut microbiota and the central nervous system. Key nutraceuticals such as probiotics, prebiotics, polyphenols, o", "journal": "Biochemical pharmacology", "date": "2026 Mar", "authors": "Ghosh N, Ghosh J, Ghosh S, Sinha K, Sil PC", "query": "huntington neuroinflammation", "discovered": "2026-03-28T11:00:51.326668", "analysis": { "category": "review", "targets": [], "compounds": [ "probiotics", "prebiotics", "polyphenols", "omega-3 fatty acids", "vitamins" ], "finding": "Nutraceuticals offer a multi-targeted approach to neuroprotection by influencing the gut-brain axis.", "relevance": "high", "repurposing_potential": true, "novel_insight": null } }, "41353868": { "pmid": "41353868", "title": "S-acylation and neuroinflammation: the therapeutic potential of zDHHC and deacylase modulation.", "abstract": "Neuroinflammation is a hallmark of many neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's disease, multiple sclerosis, and infantile neuronal ceroid lipofuscinosis. Dynamic protein S-acylation, a reversible lipid post-translational modification, is an important regulator in these processes. S-acylation is catalysed by the zDHHC palmitoyl acyltransferases, and removal of the acyl groups is mediated by acyl-protein thioesterases. S-acylation controls the localisation,", "journal": "European journal of medicinal chemistry", "date": "2026 Feb", "authors": "Duarte TA, Ng CP, Salvador JAR, Pipito L, Greaves J et al. (6 authors)", "query": "huntington neuroinflammation", "discovered": "2026-03-28T11:00:58.632454", "analysis": { "category": "review", "targets": [ "zDHHC palmitoyl acyltransferases", "acyl-protein thioesterases" ], "compounds": [], "finding": "Dysregulated S-acylation contributes to synaptic loss, aberrant immune signalling, and neurodegeneration.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41689141": { "pmid": "41689141", "title": "Mitochondrial DNA: a molecular switch driving sterile neuroinflammation.", "abstract": "Mitochondrial DNA (mtDNA) plays a pivotal role in the regulation of neuroinflammation, acting as a potent trigger of innate immune responses when released into the cytoplasm or extracellular space. mtDNA is structurally similar to bacterial DNA, containing unmethylated CpG motifs that are readily recognized by immune sensors. Under conditions of cellular stress, injury, or mitochondrial dysfunction, mtDNA can escape into the cytoplasm, where it activates the cGAS (cyclic GMP-AMP synthase)-STING ", "journal": "Translational neurodegeneration", "date": "2026 Feb", "authors": "Jauhari A, Singh T, Carlisle DL, Friedlander RM", "query": "huntington neuroinflammation", "discovered": "2026-03-28T11:01:06.985071", "analysis": { "category": "mechanism", "targets": [ "mitochondrial DNA (mtDNA)", "cGAS-STING signaling pathway", "Toll-like receptors" ], "compounds": [], "finding": "Mitochondrial DNA can trigger sterile neuroinflammation by activating the cGAS-STING signaling pathway or being detected extracellularly by Toll-like receptors.", "relevance": "high", "repurposing_potential": false, "novel_insight": "mtDNA's role in triggering sterile neuroinflammation is a novel insight" } }, "41699331": { "pmid": "41699331", "title": "Non-canonical cell death in neurodegeneration: emerging mechanisms and therapeutic Frontiers.", "abstract": "Neurodegenerative diseases, specifically Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are defined by progressively increased neuronal loss that lacks curative therapies. Increasing evidence supports that non-canonical regulated cell death pathways including ferroptosis, necroptosis, pyroptosis, and parthanatos, are implicated in pathological mechanisms of neuroinflammation, and oxidative stress, and mitochondrial dysfuncti", "journal": "Apoptosis : an international journal on programmed cell death", "date": "2026 Feb", "authors": "Ercin N, Besli N, Beker M, Celik U", "query": "huntington neuroinflammation", "discovered": "2026-03-28T11:01:15.462039", "analysis": { "category": "review", "targets": [ "ferroptosis", "necroptosis", "pyroptosis", "parthanatos" ], "compounds": [], "finding": "Non-canonical cell death pathways are implicated in neurodegenerative diseases, including Huntington's disease.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The review highlights the involvement of non-canonical cell death pathways in neurodegenerative diseases, providing a comprehensive overview of their molecular mechanisms." } }, "41672134": { "pmid": "41672134", "title": "P2X7 receptors as targets for neuroprotection.", "abstract": "In this review we explore the potential of P2X7 receptor blockers to elicit neuroprotection. This conjecture is based on a reasonably well-established role of this receptor in activating glial cells to maintain a chronic low-level neuroinflammatory state in the brain of patients suffering some neurodegenerative diseases (NDDs). In this context we briefly discuss evidence supporting the role of P2X7 receptors (P2X7) in the pathogenesis of Alzheimer's disease, Parkinson's disease, amyotrophic late", "journal": "Neuropharmacology", "date": "2026 May", "authors": "Maneu V, Garc\u00eda AG", "query": "huntington neuroinflammation", "discovered": "2026-03-28T11:01:22.280367", "analysis": { "category": "review", "targets": [ "P2X7 receptors" ], "compounds": [ "P2X7 receptor blockers" ], "finding": "P2X7 receptor blockers may elicit neuroprotection in various neurodegenerative diseases.", "relevance": "high", "repurposing_potential": true, "novel_insight": null } }, "41693955": { "pmid": "41693955", "title": "Dietary and metabolic reprogramming alleviates neurodegeneration: a review of mechanisms and clinical implications.", "abstract": "Neurodegenerative diseases, characterized by their insidious onset and progressive neuronal degeneration, present significant challenges in the fields of neuroscience and medicine. We elucidate the critical role of nutrition and cellular metabolism in the pathogenesis and progression of these disorders, with a particular focus on Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). We demonstrate that fundamental nutrients such as glucose, lipids, and amino acids ar", "journal": "Frontiers in nutrition", "date": "2026", "authors": "Fang L, Zhuang Y, Zhang M, Yang D, Zhang R et al. (7 authors)", "query": "huntington neuroinflammation", "discovered": "2026-03-28T11:01:28.626601", "analysis": { "category": "review", "targets": [], "compounds": [], "finding": "Nutrition and cellular metabolism play a critical role in the pathogenesis and progression of neurodegenerative diseases.", "relevance": "high", "repurposing_potential": false, "novel_insight": null } }, "41636944": { "pmid": "41636944", "title": "Phloretin as a Multitarget Neuroprotective Agent: Mechanistic Insights into the Modulation of Oxidative Stress, Inflammation, and Apoptosis.", "abstract": "Neurodegenerative diseases impose a substantial and growing global burden, affecting millions worldwide and leading to high medical, social, and economic costs. These are characterized by progressive neuronal dysfunction and loss, leading to cognitive, motor, and behavioral impairments. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease are driven by intertwined mechanisms of oxidative stress, neuroinflammation, protein aggregation, and neuronal", "journal": "Neuromolecular medicine", "date": "2026 Feb", "authors": "Kumari P, Singh L", "query": "huntington autophagy mTOR", "discovered": "2026-03-28T11:01:39.460873", "analysis": { "category": "small_molecule", "targets": [ "TLR-2/NF-\u03baB axis", "TLR-2/Akt/mTOR pathway" ], "compounds": [ "Phloretin" ], "finding": "Phloretin has multitarget neuroprotective effects by modulating oxidative stress, inflammation, and apoptosis.", "relevance": "high", "repurposing_potential": true, "novel_insight": "Phloretin's ability to target multiple pathways involved in neurodegenerative diseases" } }, "41787540": { "pmid": "41787540", "title": "How to improve statistical power in a trial with SCA2 patients using natural history data.", "abstract": "Randomized, double-blind, placebo-controlled trials are the gold standard for evaluating treatment effects, as they minimize biases. However, they raise ethical concerns regarding participant exposure to potentially ineffective interventions. For rare neurodegenerative diseases, these trials are further challenged by the limited number of patients. Our goal is to leverage recent advancements in statistical methodologies to enhance the statistical power of these trials. We aim to test these metho", "journal": "Trials", "date": "2026 Mar", "authors": "Tran M, Poulet PE, Petit E, Durr A, Klockgether T et al. (8 authors)", "query": "huntington digital twin clinical trial", "discovered": "2026-03-28T11:01:49.824093", "analysis": { "category": "clinical_trial", "targets": [], "compounds": [ "riluzole" ], "finding": "Researchers developed a statistical model to improve the power of clinical trials for rare neurodegenerative diseases like SCA2 using natural history data.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The study proposes leveraging recent advancements in statistical methodologies to enhance trial efficiency, rather than introducing new treatments." } }, "41933422": { "pmid": "41933422", "title": "Sex-related differences in Huntington's disease: a scoping review.", "abstract": "Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder and emerging evidence indicates sex-specific differences in disease manifestation and progression. To summarize current evidence on sex-related differences in HD across genetic, clinical, biomarker, and treatment domains and identify gaps in knowledge. A literature search was performed in PubMed and Google Scholar (up to 31.01.2026). Eligible studies examined sex- or gender-related differences in individuals with genet", "journal": "Biology of sex differences", "date": "2026 Apr", "authors": "Hemicker G, Schwarzov\u00e1 K, Cerejo C, Labrecque S, Peball M et al. (10 authors)", "query": "huntington disease treatment", "discovered": "2026-04-09T20:17:47.911465", "analysis": { "category": "review", "targets": [ "Huntington's disease (HD)" ], "compounds": [], "finding": "The review aims to summarize current evidence regarding sex-specific differences in the manifestation and progression of Huntington's disease across genetic, clinical, biomarker, and treatment domains.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The systematic scoping review specifically focuses on identifying sex-related differences in HD, which is a key area of emerging research." } }, "40874597": { "pmid": "40874597", "title": "Therapeutic strategies for Huntington's disease: current approaches and future direction.", "abstract": "Huntington's disease (HD) is an autosomal, progressive, dominant inherited neurological disorder characterized by motor dysfunction, cognitive decline, and psychiatric symptoms. HD is caused by abnormal expansion of trinucleotide CAG in exon1 of the ", "journal": "Neurodegenerative disease management", "date": "2026 Apr", "authors": "Gulzar M, Kauser S, Khan S, Adnan M, Hassan MI", "query": "huntington disease treatment", "discovered": "2026-04-09T20:17:59.193763", "analysis": { "category": "review", "targets": [ "CAG repeat expansion", "Huntingtin protein (HTT)" ], "compounds": [], "finding": "The paper reviews current and future therapeutic strategies for Huntington's disease, which is caused by an abnormal CAG trinucleotide expansion.", "relevance": "high", "repurposing_potential": false, "novel_insight": "null" } }, "41537736": { "pmid": "41537736", "title": "Rab4 spatially and functionally converges with Rab7 in the degradative endolysosomal network.", "abstract": "Rab GTPases are key regulators of endosomal trafficking in eukaryotes. In mammalian cells, Rab4 and Rab7 were shown to localize to distinct compartments, with Rab4 on early endosomes for fast recycling and Rab7 on late endosomes for degradation. Here, we show that in ", "journal": "Molecular biology of the cell", "date": "2026 Mar", "authors": "Farmer SM, Xu S, Yu Y, Ye X, Yang H et al. (19 authors)", "query": "huntington disease treatment", "discovered": "2026-04-09T20:18:13.217791", "analysis": { "category": "mechanism", "targets": [ "Rab4", "Rab7" ], "compounds": [], "finding": "The study investigates the spatial and functional convergence of Rab4 and Rab7 within the degradative endolysosomal network.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The paper suggests a functional convergence between Rab4 (typically associated with recycling) and Rab7 (associated with degradation) in the endolysosomal network." } }, "40517187": { "pmid": "40517187", "title": "Crossing the blood-brain barrier: nanoparticle-based strategies for neurodegenerative disease therapy.", "abstract": "Neurodegenerative conditions, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's disease, represent a critical medical challenge due to their increasing prevalence, severe consequences, and absence of curative treatments. Beyond the need for a deeper understanding of the fundamental mechanisms underlying neurodegeneration, the development of effective treatments is hindered by the blood-brain barrier, which poses a major obstacle to delivering therapeutic agents ", "journal": "Drug delivery and translational research", "date": "2026 Mar", "authors": "Haro-Mart\u00ednez E, Muscolino E, Moral N, Duran J, Fornaguera C", "query": "huntington disease treatment", "discovered": "2026-04-09T20:18:26.072503", "analysis": { "category": "review", "targets": [ "neurodegenerative diseases" ], "compounds": [ "nanoparticles" ], "finding": "Nanoparticle-based strategies are being reviewed as a method to overcome the blood-brain barrier for treating various neurodegenerative diseases.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The review focuses on the general application of nanoparticles to overcome the BBB rather than a specific novel mechanism or compound." } }, "40313114": { "pmid": "40313114", "title": "Inherent potential of mitochondria-targeted interventions for chronic neurodegenerative diseases.", "abstract": "The cure rate for chronic neurodegenerative diseases remains low, creating an urgent need for improved intervention methods. Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases. This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases, aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options. We detail five targeted mitochondr", "journal": "Neural regeneration research", "date": "2026 Apr", "authors": "Zhou M, Zheng M, Liang S, Li M, Ma J et al. (11 authors)", "query": "huntington disease gene therapy", "discovered": "2026-04-09T20:18:46.792910", "analysis": { "category": "review", "targets": [ "mitochondrial function", "mitophagy", "mitochondrial fission", "mitochondrial biogenesis" ], "compounds": [], "finding": "Targeted mitochondrial interventions represent a promising area for treating chronic neurodegenerative diseases by addressing underlying mitochondrial dysfunction.", "relevance": "high", "repurposing_potential": true, "novel_insight": "The paper comprehensively reviews five distinct, actionable strategies (mitophagy promotion, fission inhibition, biogenesis enhancement, antioxidant application, and mitochondrial transplantation) for intervention." } }, "40536996": { "pmid": "40536996", "title": "Neuroglobin: A promising candidate to treat neurological diseases.", "abstract": "Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide. Altogether, the burden of neurological disorders has increased considerably over the past 30 years because of population aging. Overall, neurological diseases significantly impair cognitive and motor functions and their incidence will increase as societies age and the world's population continues to grow. Autism spectru", "journal": "Neural regeneration research", "date": "2026 Apr", "authors": "Ya\u00f1ez IM, Torres-Cuevas I, Corral-Debrinski M", "query": "huntington disease gene therapy", "discovered": "2026-04-09T20:18:59.119248", "analysis": { "category": "review", "targets": [ "Neuroglobin" ], "compounds": [], "finding": "The paper discusses the general burden of neurological disorders, listing Huntington's disease among many conditions caused by cellular homeostasis perturbations.", "relevance": "medium", "repurposing_potential": true, "novel_insight": "null" } }, "41926793": { "pmid": "41926793", "title": "Extensive transcriptomic changes in cellular and animal models of Huntington's disease depending on the length of CAG repeats in the exon 1 of the HTT gene.", "abstract": "Although Huntington's disease - a severe, inherited, neurodegenerative disorder - is primarily caused by a pathological variant of the HTT gene (encoding huntingtin protein) which is characterized by the extension of CAG repeats in the 1st exon exceeding 36 triplets, the biochemical mechanisms underlying the disease remain poorly understood. Mutant huntingtin forms toxic aggregates in cells; however, the clinical symptoms usually appear in adulthood. Recent reports suggested that somatic expansi", "journal": "Biochemical and biophysical research communications", "date": "2026 Apr", "authors": "Szulc A, Walter BM, Gaffke L, Wi\u015bniewska K, \u017babi\u0144ska M et al. (12 authors)", "query": "huntington somatic expansion CAG", "discovered": "2026-04-09T20:19:20.491768", "analysis": { "category": "mechanism", "targets": [ "HTT gene", "CAG repeats" ], "compounds": [], "finding": "The transcriptomic changes in cellular and animal models of Huntington's disease are dependent on the length of the CAG repeats in the HTT gene.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The study highlights the role of CAG repeat length in determining the transcriptomic profile, suggesting a dose-dependent mechanism for pathogenicity." } }, "41925063": { "pmid": "41925063", "title": "Combination Disease-Modifying Therapy for Neurodegenerative Diseases Using Repurposed Drugs.", "abstract": "We review the positive effects of several existing drugs from different classes, such as chemical chaperones, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), iron chelators, and cluster-Abelson tyrosine kinase inhibitors (c-Abl TKIs), in preclinical disease models and in available published human data following use of these drugs in individuals with common neurodegenerative diseases (NDs), including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), a", "journal": "Annals of neurology", "date": "2026 Apr", "authors": "Shtilbans A, Lang AE", "query": "huntington drug repurposing", "discovered": "2026-04-09T20:19:45.582283", "analysis": { "category": "review", "targets": [ "multiple pathogenic processes involved in neurodegeneration" ], "compounds": [ "chemical chaperones", "glucagon-like peptide-1 receptor agonists (GLP-1 RAs)", "iron chelators", "cluster-Abelson tyrosine kinase inhibitors (c-Abl TKIs)" ], "finding": "The paper reviews the positive effects of various existing drugs from different classes for treating multiple neurodegenerative diseases, including Huntington's disease.", "relevance": "high", "repurposing_potential": true, "novel_insight": "The paper proposes a strategy to design an ideal combination of drugs to address multiple pathogenic processes in neurodegeneration." } }, "41591821": { "pmid": "41591821", "title": "From Cancer to Neuroprotection: Pazopanib Modulates the RIPK1/RIPK3/MLKL and PGAM5/DRP1 Pathways in 3- Nitropropionic Acid-Induced Huntington's Disease.", "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder with a poorly understood neurobiological basis. Among the various forms of programmed cell death implicated in neurodegeneration, necroptosis has recently garnered significant attention. Notably, dysregulated necroptosis provokes immune response that drives excessive pro-inflammatory cytokine production, promoting further necroptotic cell death through TNF-\u03b1/RIPK1 signaling. Consequently, necroptosis exacerbates neuroinflammat", "journal": "Drug development research", "date": "2026 Apr", "authors": "Eltarzy MA, Rabie MA, Sayed RH, Ahmed MAE, Ahmedy OA", "query": "huntington drug repurposing", "discovered": "2026-04-09T20:20:07.129212", "analysis": { "category": "mechanism", "targets": [ "RIPK1", "RIPK3", "MLKL", "PGAM5", "DRP1" ], "compounds": [ "Pazopanib" ], "finding": "Pazopanib modulates the RIPK1/RIPK3/MLKL and PGAM5/DRP1 pathways, suggesting a role in mitigating necroptosis and mitochondrial dysfunction in HD.", "relevance": "high", "repurposing_potential": true, "novel_insight": "The study links an anti-cancer agent (Pazopanib) to modulating specific necroptotic and mitochondrial pathways (RIPK1/RIPK3/MLKL and PGAM5/DRP1) in the context of HD pathogenesis." } }, "41951733": { "pmid": "41951733", "title": "Population-scale repeat expansions elucidate disease risk and brain atrophy.", "abstract": "Pathogenic expansions of short tandem repeats (STRs) cause over 70 neurological diseases", "journal": "Nature", "date": "2026 Apr", "authors": "Pounraja VK, Sul JH, Herman J, O'Keeffe S, Rajagopal V et al. (35 authors)", "query": "huntington biomarker neurofilament", "discovered": "2026-04-09T20:20:20.680341", "analysis": { "category": "review", "targets": [ "CAG repeat expansions" ], "compounds": [], "finding": "The study analyzes population-scale repeat expansions to elucidate disease risk and associated brain atrophy in Huntington's disease.", "relevance": "high", "repurposing_potential": false, "novel_insight": "Focus on population-scale analysis linking repeat expansions directly to measurable brain atrophy." } }, "41944829": { "pmid": "41944829", "title": "Quantifying brain-age gap in people with HIV on antiretroviral therapy using plasma neurofilament light chain.", "abstract": "To estimate the number of additional years above chronological age (\"brain-age gap\") at which observed plasma neurofilament light chain (NfL) levels in cognitively unimpaired people with HIV (PWH) correspond to published age-stratified standards from cognitively unimpaired individuals in the general population. Secondary analysis of the multicenter observational cohort study (ACTG HAILO) involving older, cognitively unimpaired PWH on antiretroviral therapy (ART). Plasma NfL concentrations were q", "journal": "AIDS (London, England)", "date": "2026 Apr", "authors": "Park H, Hyle EP, Tassiopoulos KK, Gissl\u00e9n M, Rubin LH et al. (7 authors)", "query": "huntington biomarker neurofilament", "discovered": "2026-04-09T20:20:37.213091", "analysis": { "category": "biomarker", "targets": [ "neurofilament light chain (NfL)" ], "compounds": [], "finding": "Plasma NfL levels in cognitively unimpaired people with HIV can be used to estimate a 'brain-age gap' by comparing them to age-stratified general population standards.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The application of NfL to quantify brain-age gap specifically in the context of HIV infection and ART treatment." } }, "41930586": { "pmid": "41930586", "title": "AI-Driven Biomarker Discovery in Motor-Related Neurodegenerative Diseases.", "abstract": "Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and spinocerebellar ataxias (SCAs) are examples of neurodegenerative disorders (NDDs) that share overlapping neuropathological processes and largely affect motor coordination. For early diagnosis, illness monitoring, and treatment targeting, it is essential to find trustworthy biomarkers that represent motor circuit dysfunction. The purpose of this study is to summarize the state of the art regarding molecu", "journal": "CNS & neurological disorders drug targets", "date": "2026 Mar", "authors": "Pavithra N, Begum RF, Ashwini ST, Nirenjen S, Singh A et al. (8 authors)", "query": "huntington biomarker neurofilament", "discovered": "2026-04-09T20:20:55.203762", "analysis": { "category": "review", "targets": [ "motor circuit dysfunction", "molecular biomarkers", "neurochemical biomarkers", "imaging biomarkers" ], "compounds": [], "finding": "The study reviews current molecular, neurochemical, and imaging biomarkers for motor impairment in NDDs and explores the application of AI/ML for their discovery and validation.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The systematic investigation of AI/ML applications across multiple motor-related NDDs (PD, HD, ALS, SCAs) for biomarker discovery." } }, "41915164": { "pmid": "41915164", "title": "Spontaneous speech and language measures as predictive biomarkers of clinically meaningful disease progression and neurodegeneration in Huntington's disease.", "abstract": "Huntington's disease (HD) is characterized by heterogeneous rates of clinical progression, complicating patient monitoring and clinical trial design. Although speech and language alterations are increasingly recognized as part of the HD cognitive phenotype, their value as short-term prognostic biomarkers of clinically meaningful disease progression and neurodegeneration remains unestablished. In this prospective 12-month longitudinal study, we investigated whether objectively quantified spontane", "journal": "Journal of neural transmission (Vienna, Austria : 1996)", "date": "2026 Mar", "authors": "Puig-Davi A, Franch-Marti C, Caler-Gameiro L, Perez-Perez J, Olmedo-Saura G et al. (17 authors)", "query": "huntington biomarker neurofilament", "discovered": "2026-04-09T20:21:11.614723", "analysis": { "category": "biomarker", "targets": [ "spontaneous speech and language measures" ], "compounds": [], "finding": "Objectively quantified spontaneous speech and language measures were investigated as potential short-term prognostic biomarkers for clinically meaningful disease progression and neurodegeneration in Huntington's disease.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The study focuses on establishing the predictive value of *spontaneous* speech and language measures, rather than just standardized testing, for tracking short-term progression." } }, "41951144": { "pmid": "41951144", "title": "Longitudinal and combined assessment of 24(S)-hydroxycholesterol and Neurofilament light chain in the early stages of Huntington's disease.", "abstract": "Huntington's Disease (HD) is an autosomal dominant neurodegenerative disorder. Recent clinical research has focused on neurofilament light chain protein (NfL), and cholesterol metabolites as potential fluid biomarkers related to disease progression. Our aim was to explore whether the combined longitudinal assessment of NfL and cholesterol-derived metabolites would improve the characterization of early HD stages. We enrolled 96 HD individuals and 63 healthy controls. Disease stage of HD participa", "journal": "Neurobiology of disease", "date": "2026 Apr", "authors": "Sarro L, Valenza M, Mongelli A, Passoni A, Castaldo A et al. (20 authors)", "query": "huntington biomarker neurofilament", "discovered": "2026-04-09T20:21:27.476017", "analysis": { "category": "biomarker", "targets": [ "Neurofilament light chain (NfL)", "24(S)-hydroxycholesterol" ], "compounds": [], "finding": "The study aimed to determine if combining longitudinal assessments of NfL and cholesterol metabolites could improve the characterization of early Huntington's disease stages.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The combination of NfL and cholesterol metabolites for longitudinal assessment in early HD stages." } }, "41918200": { "pmid": "41918200", "title": "Neuroinflammation, Autophagy, and Neurodegeneration: Mechanisms and Therapeutic Insights.", "abstract": "Neuroinflammation and autophagy dysregulation are critical in the pathogenesis of neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's disease. Neuroinflammation occurs after a sustained immune response, which transitions into a chronic pathological state, leading to the sustained generation of pro-inflammatory cytokines and oxidative stress, causing neuronal damage. Meanwhile, defective autophagy exacerbates disease by promoting protein accumulation, e.g., amyloid-\u03b2, tau, ", "journal": "CNS & neurological disorders drug targets", "date": "2026 Mar", "authors": "Khanal P, Balmik A", "query": "huntington CRISPR", "discovered": "2026-04-09T20:21:44.420835", "analysis": { "category": "review", "targets": [ "mTOR", "AMPK", "pro-inflammatory cytokines", "oxidative stress" ], "compounds": [], "finding": "Neuroinflammation and defective autophagy create a vicious cycle that drives neuronal damage in Huntington's disease.", "relevance": "high", "repurposing_potential": true, "novel_insight": "The paper synthesizes the interplay between mTOR/AMPK regulation, inflammation, and autophagy specifically in the context of HD pathogenesis." } }, "41919473": { "pmid": "41919473", "title": "Long non-coding RNAs in neurodegenerative diseases - Molecular mechanisms, liquid biopsy biomarkers, and therapeutic targets: A review.", "abstract": "Neurodegenerative diseases (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), are age-related disorders characterized by progressive neuronal loss, cognitive decline, and limited options for disease-modifying treatments. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play significant roles in neurodevelopment, neuronal homeostasis, and disease progression; however, their involvement in shared p", "journal": "Biomolecules & biomedicine", "date": "2026 Mar", "authors": "Cheng Y, Qiu M, Yu Z, Tang X, Zhang J", "query": "huntington antisense oligonucleotide", "discovered": "2026-04-09T20:22:05.882431", "analysis": { "category": "review", "targets": [ "long non-coding RNAs (lncRNAs)", "neuronal homeostasis", "pathogenic pathways" ], "compounds": [], "finding": "lncRNAs are implicated in the pathogenesis of multiple neurodegenerative diseases, including Huntington's disease, by modulating common disease mechanisms.", "relevance": "high", "repurposing_potential": true, "novel_insight": "The review consolidates findings across multiple methodologies (experimental, transcriptomic, bioinformatic) to define the role of lncRNAs in shared pathogenic pathways of NDDs." } }, "41287980": { "pmid": "41287980", "title": "Quantitative relationship between tominersen concentrations in cerebrospinal fluid and biomarker changes in Huntington's disease patients.", "abstract": "Intrathecally administered antisense oligonucleotide tominersen aims to slow Huntington's disease progression by lowering mutant huntingtin (mHTT) protein levels. This study used non-linear mixed effects population pharmacokinetic and pharmacodynamic (PKPD) modelling to characterize the relationship between tominersen concentration in cerebrospinal fluid (CSF) and CSF mHTT reduction. Additionally, the relationship between tominersen CSF exposure and changes in other CSF biomarkers was investigat", "journal": "British journal of clinical pharmacology", "date": "2026 Apr", "authors": "Yamamoto Y, Silber Baumann HE, Bj\u00f6rnsson M, Grimsey P, Hawellek DJ et al. (12 authors)", "query": "huntington antisense oligonucleotide", "discovered": "2026-04-09T20:22:20.916513", "analysis": { "category": "aso", "targets": [ "mutant huntingtin (mHTT)" ], "compounds": [ "tominersen" ], "finding": "The study characterized the relationship between tominersen concentration in cerebrospinal fluid and the reduction of CSF mHTT using non-linear mixed effects PKPD modeling.", "relevance": "high", "repurposing_potential": false, "novel_insight": "Application of non-linear mixed effects PKPD modeling to precisely link CSF drug exposure to biomarker changes for dose selection in a major ongoing trial." } }, "40145977": { "pmid": "40145977", "title": "Potential targets of microglia in the treatment of neurodegenerative diseases: Mechanism and therapeutic implications.", "abstract": "For diverse neurodegenerative disorders, microglial cells are activated. Furthermore, dysfunctional and hyperactivated microglia initiate mitochondrial autophagy, oxidative stress, and pathological protein accumulation, ending with neuroinflammation that exacerbates damage to dopaminergic neurons and contributes significantly to the pathology of neurodegenerative disorder. Microglial over-activation is closely associated with the secretion of pro-inflammatory cytokines, the phagocytosis of injur", "journal": "Neural regeneration research", "date": "2026 Apr", "authors": "Zhao W, Liu Z, Wu J, Liu A, Yan J", "query": "huntington neuroinflammation", "discovered": "2026-04-09T20:22:38.374266", "analysis": { "category": "review", "targets": [ "microglia", "mitochondrial autophagy", "oxidative stress", "pro-inflammatory cytokines" ], "compounds": [], "finding": "Microglial dysfunction, characterized by hyperactivation, contributes significantly to neurodegeneration through oxidative stress, mitochondrial autophagy, and neuroinflammation.", "relevance": "high", "repurposing_potential": true, "novel_insight": "The review summarizes the general role of microglia across multiple neurodegenerative diseases rather than focusing on a single novel mechanism or target." } }, "41885638": { "pmid": "41885638", "title": "Cryptoxanthin as a multitarget neuroprotective agent: mechanistic and in silico perspectives.", "abstract": "Neurodegenerative diseases such as Parkinson's disease (PD), Huntington's disease (HD), Alzheimer's disease (AD), and Amyotrophic lateral sclerosis (ALS) are complex disorders driven by multiple pathological processes, including oxidative stress, mitochondrial dysfunction, protein misfolding, and neuroinflammation. Due to this multifactorial nature, there is a growing interest in identifying natural compounds with multi-targeted neuroprotective properties. This review aims to evaluate the therap", "journal": "The Journal of pharmacy and pharmacology", "date": "2026 Mar", "authors": "Sadhukhan A, Chauhan A, Kumar M, Singh TG, Mujwar S et al. (6 authors)", "query": "huntington neuroinflammation", "discovered": "2026-04-09T20:22:54.671022", "analysis": { "category": "review", "targets": [ "oxidative stress", "mitochondrial dysfunction", "protein misfolding", "neuroinflammation" ], "compounds": [ "\u03b2-cryptoxanthin" ], "finding": "\u03b2-cryptoxanthin shows potential as a multi-targeted neuroprotective agent for various neurodegenerative diseases.", "relevance": "high", "repurposing_potential": true, "novel_insight": "The review focuses on evaluating the broad, multi-targeted neuroprotective potential of a natural carotenoid, \u03b2-cryptoxanthin, rather than a specific mechanism or genetic pathway." } }, "42035261": { "pmid": "42035261", "title": "Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.", "abstract": "Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expansion of a CAG trinucleotide repeat in the huntingtin (HTT) gene, which leads to a mutant protein that destroys neurons in the brain. Despite intense effort, there remains no approved disease-modifying therapy for HD. Here we develop a pan-HTT-targeting CRISPR-Cas9 system that, when delivered to the striatum of R6/2 and YAC128 mice by AAV5, lowered mutant HTT mRNA and protein by 55-80% via its induction of fram", "journal": "Molecular therapy : the journal of the American Society of Gene Therapy", "date": "2026 Apr", "authors": "Tan K, Del Bosque Siller D, Xiong AY, Wang AXA, McCallister TX et al. (16 authors)", "query": "huntington disease treatment", "discovered": "2026-04-30T07:14:06.508399", "analysis": { "category": "crispr", "targets": [ "HTT" ], "compounds": [ "CRISPR-Cas9", "AAV5" ], "finding": "A pan-HTT-targeting CRISPR-Cas9 system successfully reduced mutant HTT mRNA and protein levels by 55-80% and significantly improved motor and behavioral phenotypes in mouse models of HD.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The successful development of a pan-HTT-targeting CRISPR system that achieves significant molecular knockdown and functional behavioral rescue in vivo." } }, "41552385": { "pmid": "41552385", "title": "An acyclic nucleic acid-modified siRNA targeting CAG expansions for polyglutamine disease treatment.", "abstract": "Polyglutamine (polyQ) diseases are inherited neurological disorders caused by an expansion of the cytosine-adenine-guanine (CAG) repeat in the causative genes. These include Huntington's disease, spinal and bulbar muscular atrophy (SBMA), and spinocerebellar ataxias (SCAs). Clinical trials have been conducted using nucleic acid therapeutics to silence the causative gene for these diseases, but none have been approved for use. Furthermore, while oligonucleotides targeting the CAG repeats are an a", "journal": "Molecular therapy. Nucleic acids", "date": "2026 Mar", "authors": "Maeda K, Hirunagi T, Sahashi K, Kamiya Y, Iida M et al. (12 authors)", "query": "huntington disease treatment", "discovered": "2026-04-30T07:14:48.027042", "analysis": { "category": "aso", "targets": [ "CAG repeat expansion", "polyglutamine genes" ], "compounds": [ "acyclic serinol nucleic acid (SNA)-modified siRNA" ], "finding": "The study developed an acyclic serinol nucleic acid (SNA)-modified siRNA designed to specifically target pathogenic CAG repeats for polyglutamine disease treatment.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The use of SNA modification in the siRNA structure is novel, aiming to improve specificity and prevent concomitant silencing of the wild-type allele." } }, "42041587": { "pmid": "42041587", "title": "Gene Editing Strategies for Neurological and Mental Disorders: Advances in Delivery, Methodology, and Clinical Translation.", "abstract": "Neurological and mental disorders are among the main causes of disability worldwide, affecting over three billion people and increasing the socioeconomic burden. Advances in molecular genetics and genome engineering have led to gene-targeted therapies that address root causes rather than just symptoms. This review covers current genome-editing tools, including CRISPR/Cas, base editing, and prime editing. The focus is on the benefits of gene editing in the central nervous system, where post-mitot", "journal": "Cells", "date": "2026 Apr", "authors": "Elias A, Stern S", "query": "huntington disease gene therapy", "discovered": "2026-04-30T07:15:36.897978", "analysis": { "category": "review", "targets": [ "neurological disorders", "mental disorders", "gene targets" ], "compounds": [ "CRISPR/Cas", "base editing", "prime editing", "viral vectors", "nanoparticles", "exosomes" ], "finding": "Gene editing tools offer a lasting, root-cause therapeutic approach for CNS disorders, contingent upon effective delivery across the blood-brain barrier.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The integration of advanced editing techniques (prime/base editing) with non-viral delivery systems (nanoparticles/exosomes) to overcome the blood-brain barrier represents a major translational advance." } }, "42037491": { "pmid": "42037491", "title": "Iloperidone treatment mitigates the Juvenile Huntington's Disease phenotype possibly via Sigma-1 Receptor Modulation.", "abstract": "Juvenile Huntington's disease (jHD) is a severe genetic disorder with combined neurodegenerative and neurodevelopmental features, characterized by early onset and markedly reduced life expectancy. Despite extensive efforts, drug development has been largely unsuccessful and no effective therapy capable of mitigating the pathological phenotype is currently available. Here, we investigated the potential of the FDA-approved drug iloperidone to ameliorate disease-related phenotypes in cortical neuro", "journal": "The FEBS journal", "date": "2026 Apr", "authors": "Fornetti E, Galluzzi G, Frezzini M, Exertier C, Brufani V et al. (12 authors)", "query": "huntington disease gene therapy", "discovered": "2026-04-30T07:16:08.205330", "analysis": { "category": "small_molecule", "targets": [ "Sigma-1 Receptor (S1R)" ], "compounds": [ "Iloperidone" ], "finding": "Iloperidone treatment showed potential to ameliorate juvenile Huntington's disease phenotypes in patient-derived cortical neurons, possibly through Sigma-1 Receptor modulation.", "relevance": "high", "repurposing_potential": true, "novel_insight": "The investigation proposes that the therapeutic effect of the existing drug iloperidone in jHD is mediated by activating S1R-dependent proteostasis pathways." } }, "42007924": { "pmid": "42007924", "title": "Towards AI-driven prediction of HTT CAG size in super-expanded human spiny projection neurons from Huntington disease donors.", "abstract": "Somatic instability (SI) of the CAG tract in HTT is a major driver of neurodegeneration of Spiny Projection Neurons (SPNs), the primary neuronal subtype affected in Huntington's disease (HD). SPNs can accumulate hundreds of CAG repeats during a patient's lifetime, and once the expansion exceeds \u223c150 CAGs, they acquire distinct, cell-autonomous transcriptional alterations that ultimately contribute to degeneration. Here, we developed the \"HD-Phase-Model\", a mathematical framework designed to iden", "journal": "Journal of Huntington's disease", "date": "2026 Apr", "authors": "Maestri S, Scalzo D, Zobel M, Besusso D, Cattaneo E", "query": "huntington somatic expansion CAG", "discovered": "2026-04-30T07:16:48.044988", "analysis": { "category": "ai_ml", "targets": [ "HTT", "CAG tract" ], "compounds": [], "finding": "A mathematical framework, the HD-Phase-Model, was developed to identify super-expanded Spiny Projection Neurons based solely on their transcriptional profile, bypassing the need for direct CAG repeat sizing.", "relevance": "high", "repurposing_potential": false, "novel_insight": "The model successfully links the pathological state of super-expansion (a physical characteristic) to distinct transcriptional alterations using only single-nucleus transcriptomic data, which is a significant advancement over methods requiring direct repeat sizing." } }, "41925785": { "pmid": "41925785", "title": "Psychosis in Huntington disease: a short update.", "abstract": "", "journal": "Journal of neural transmission (Vienna, Austria : 1996)", "date": "2026 Apr", "authors": "Jellinger KA", "query": "huntington disease treatment", "discovered": "2026-05-05T15:33:59.514573", "analysis": null }, "41977460": { "pmid": "41977460", "title": "Usefulness of C. elegans Models of Alzheimer's and Huntington's Disease to Evaluate Novel Imidazoline I2 Receptor Ligands.", "abstract": "Neurodegenerative diseases such as Alzheimer's (AD) and Huntington's (HD) remain major therapeutic challenges due to limited treatment efficacy. Imidazoline I2 receptor (I2-IR) ligands have recently emerged as promising neuroprotective agents, with reported roles in modulating oxidative stress, neuroinflammation, and protein aggregation. This study evaluates the therapeutic potential of several I2-IR ligands, including Idazoxan, CR4056, and novel compounds, using Caenorhabditis elegans (C. elega", "journal": "International journal of molecular sciences", "date": "2026 Apr", "authors": "Taboada-Jara T, Ribalta M, Romero-Becerra F, Muix\u00ed J, Bellver-Sanchis A et al. (8 authors)", "query": "huntington disease treatment", "discovered": "2026-05-05T15:34:01.522204", "analysis": null }, "41651710": { "pmid": "41651710", "title": "Safety and efficacy of VMAT2 inhibitors in Huntington Disease: A systematic review.", "abstract": "Chorea affects quality of life and functional independence in most adults with Huntington disease (HD). Vesicular monoamine transporter 2 (VMAT2) inhibitors, tetrabenazine, deutetrabenazine, and valbenazine, are pharmacological agents used to manage HD-related chorea. This systematic review evaluates the safety and efficacy of these agents in individuals with HD. This review was conducted in accordance with PRISMA guidelines and registered with PROSPERO, CRD42024581306. A comprehensive literatur", "journal": "Parkinsonism & related disorders", "date": "2026 Apr", "authors": "Baghaei A, Dehnavi AZ, Hashempour Z, Bordelon Y, Jimenez-Shahed J et al. (8 authors)", "query": "huntington disease treatment", "discovered": "2026-05-05T15:34:03.531550", "analysis": null }, "41967079": { "pmid": "41967079", "title": "Stem cells enhance mitochondrial function in experimental Huntington's disease.", "abstract": "Huntington's Disease (HD) is a neurodegenerative disorder caused by CAG triplet expansion in the HTT gene, producing a mutant Huntingtin protein that impairs mitochondrial dynamics by reducing fusion and increasing fission. Mesenchymal stem cells (MSCs) have shown potential therapeutic effects by sharing functional mitochondria and other secretomes. In this study, quinolinic acid-lesioned neuro-2a (QA-N2a) cells and glutamatergic neurons with 50 CAG repeats (HD neurons) were co-cultured with hum", "journal": "Stem cells (Dayton, Ohio)", "date": "2026 Apr", "authors": "D'Egidio F, Putthanbut N, Starahs M, Lee JY, Borlongan CV", "query": "huntington disease treatment", "discovered": "2026-05-05T15:34:05.539101", "analysis": null }, "42048072": { "pmid": "42048072", "title": "[Huntington\u00b4s disease - overview].", "abstract": "Huntington's disease (HD) is a rare, autosomal dominant neurodegenerative disorder characterized by progressive movement disturbances, psychiatric symptoms, and cognitive impairment. The disease is caused by an increased number of repeats of the cytosine-adenine-guanine (CAG) base sequence in the HTT gene, leading to the production of a huntingtin protein with toxic gain-of-function properties and the accumulation of protein aggregates in neurons, resulting in neurodegeneration. The prevalence o", "journal": "Laeknabladid", "date": "2026 May", "authors": "Briem S, Bjornsson T, Stefansdottir V, Jonsson JJ, Sveinsson OA", "query": "huntington disease gene therapy", "discovered": "2026-05-05T15:34:09.986744", "analysis": null }, "41977320": { "pmid": "41977320", "title": "Polyfunctionalized N-Arylsulfonyl Indoles: Identification of (E)-N-Hydroxy-3-{3-[(5-(3-(piperidin-1-yl)propoxy]-1H-indol-1-yl)sulfonyl]phenyl}acrylamide (MTP150) for the Epigenetic-Based Therapy of Parkinson's Disease.", "abstract": "Herein, we have identified the polyfunctionalized 1-(phenylsulfonyl)-1H-indole-2-carboxylic acid derivative MTP150 for the treatment of neurodegenerative diseases owing to its efficacy in reducing protein aggregation, modulating matrix metalloproteinase activity, mitigating neuroinflammation, and enhancing DNA damage repair pathways across in vivo Caenorhabditis elegans models of Alzheimer's disease, Parkinson's disease (PD), and Huntington's disease. Further experiments in an in vivo Drosophila", "journal": "International journal of molecular sciences", "date": "2026 Mar", "authors": "Toledano-Pinedo M, Porro-P\u00e9rez A, Sch\u00e4ker-H\u00fcbner L, Diez-Iriepa D, Iriepa I et al. (28 authors)", "query": "huntington disease gene therapy", "discovered": "2026-05-05T15:34:11.993428", "analysis": null }, "41906693": { "pmid": "41906693", "title": "Inhibition of the NLRP3 Inflammasome With MCC950 Improves Gut Health in Huntington's Disease Mice.", "abstract": "Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder featuring abnormal cognition, psychiatric symptoms, movement, and gastrointestinal function. It is caused by a tandem-repeat gene mutation encoding an expanded polyglutamine tract in the huntingtin protein. Our group was the first to demonstrate gut microbial disruption in both clinical HD cohorts and validated preclinical models, supporting a role for microbiota-gut-brain axis dysfunction in HD. The NLRP3 inflammasome", "journal": "Journal of neurochemistry", "date": "2026 Apr", "authors": "Sarkar SK, Ekwudo MN, Lu D, Masson B, Kiridena P et al. (11 authors)", "query": "huntington disease gene therapy", "discovered": "2026-05-05T15:34:14.003939", "analysis": null }, "42061810": { "pmid": "42061810", "title": "UNEXPECTED MECHANISMS OF REPURPOSED DRUGS IN THE PATHOGENIC PATHWAYS OF NEURODEGENERATIVE DISEASES. DISCOVERING NEW NEUROPROTECTIVE THERAPIES IN CELLULAR MODELS.", "abstract": "Advances in biomedicine have increased life expectancy, leading to a growing prevalence of age-related neurodegenerative diseases such as Alzheimer's and Parkinson's disease, alongside disorders of genetic or environmental origin including multiple sclerosis, Huntington's disease, and amyotrophic lateral sclerosis. Despite their diverse etiologies, these conditions share convergent pathogenic mechanisms-calcium overload, neuroinflammation, and oxidative stress-that drive neuronal apoptosis and p", "journal": "Neuropharmacology", "date": "2026 Apr", "authors": "Arasmou-Idrovo MS, Mar\u00edn-Rodr\u00edguez B, Gironda-Mart\u00ednez A, Garc\u00eda AG, Le\u00f3n R et al. (7 authors)", "query": "huntington drug repurposing", "discovered": "2026-05-05T15:34:18.598971", "analysis": null }, "41977439": { "pmid": "41977439", "title": "Targeting Non-Coding RNAs as a Potential Therapeutic and Delivery Strategy Against Neurodegenerative Diseases.", "abstract": "Neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS), represent a growing global health challenge characterized by progressive neuronal loss and a lack of definitive disease-modifying treatments. This review explores the emerging potential of targeting non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and exosomal RNAs, to modulate pathogenic molecular pathways and a", "journal": "International journal of molecular sciences", "date": "2026 Apr", "authors": "Bougea A", "query": "huntington CRISPR", "discovered": "2026-05-05T15:34:23.259473", "analysis": null }, "42049145": { "pmid": "42049145", "title": "Humanized mice carrying a pathogenic GRN deletion as a pre-clinical platform for targeted gene therapies in frontotemporal dementia.", "abstract": "Frontotemporal dementia (FTD) is an early onset dementia characterized by neuropathology and changes to patient behaviour. Haploinsufficiency of the gene progranulin (GRN) is a major cause of FTD, for which there are no effective therapies. Corrective gene therapies that restore GRN expression are of clinical interest, but current in vivo systems have limitations. We developed a novel strain of mice expressing a human GRN transgene bearing a four base pair deletion in exon 5 (GRNc.388_391delCAGT", "journal": "Neurobiology of disease", "date": "2026 Apr", "authors": "Life BE, Kazemian P, Petkau TL, de Moura Gomes A, Thomson SB et al. (13 authors)", "query": "huntington CRISPR", "discovered": "2026-05-05T15:34:25.266928", "analysis": null }, "42009995": { "pmid": "42009995", "title": "Exploring the role of tocotrienol-rich fraction (TRF) in ameliorating neuroinflammation.", "abstract": "Neuroinflammation is a chronic inflammatory response that contributes to synaptic dysfunction and neuronal damage, it is a common feature among various neurodegenerative diseases such as Alzheimer's Disease (AD), Parkinson's Disease (PD) and Huntington's Disease (HD). Tocotrienol-rich fraction (TRF) is a form of vitamin E that is known for its anti-inflammatory, antioxidant and neuroprotective properties. Yet, it has not been adequately investigated in both cellular and animal neuroinflammation ", "journal": "Inflammopharmacology", "date": "2026 Apr", "authors": "Tan JY, Retinasamy T, Lee VLL, Radhakrishnan AK, Yeong KY", "query": "huntington neuroinflammation", "discovered": "2026-05-05T15:34:29.914057", "analysis": null }, "42031349": { "pmid": "42031349", "title": "Propagation of gut-injected AAV2/1-Htt171-82Q to the brain induces Huntington's disease-like pathology.", "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder that leads to thbe production of pathogenic mutant huntingtin (mHtt) protein and is characterized by motor and psychiatric symptoms. While HD has classically been studied as a brain-centered condition, emerging research indicates that the gut-brain axis may play a role in disease initiation and progression. However, direct experimental evidence demonstrating a peripheral-to-central route for mHtt propagation remains limited an", "journal": "Neurobiology of disease", "date": "2026 Apr", "authors": "Islam J, Kc E, Chaudhary PK, Ali M, Abbas H et al. (8 authors)", "query": "huntington neuroinflammation", "discovered": "2026-05-05T15:34:31.924150", "analysis": null }, "41771688": { "pmid": "41771688", "title": "Metformin improves RAN protein pathology, alternative splicing, and behavioral phenotypes in SCA8 mice.", "abstract": "Spinocerebellar ataxia type 8 (SCA8) is a member of a group of dominantly inherited, debilitating neurological diseases caused by CAG\u2022CTG expansions for which there are no effective treatments. RAN translation, which was discovered in SCA8, has previously been shown to occur across CAG and CUG expansion transcripts, making treatments for SCA8 potentially relevant to a broad group of diseases, including SCA1, SCA2, SCA3, SCA6, SCA7, SCA12, Huntington's disease, and myotonic dystrophy type 1. In a", "journal": "Life science alliance", "date": "2026 May", "authors": "Romano LE, Tsukagoshi S, Davey-Osuch EE, Ajredini R, Manasi K et al. (13 authors)", "query": "huntington neuroinflammation", "discovered": "2026-05-05T15:34:33.930880", "analysis": null }, "41796789": { "pmid": "41796789", "title": "Effects of different exercise modalities on four major neurodegenerative diseases and their molecular mechanisms.", "abstract": "Neurodegenerative diseases are marked by progressive neuronal damage and currently lack a cure. Recently, exercise has emerged as a promising non-pharmacological approach to potentially slow disease progression and enhance cognitive function. This narrative review summarizes the effects of various exercise modalities-including aerobic exercise, resistance training, and balance training-on four major neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, and s", "journal": "Neuroscience", "date": "2026 May", "authors": "Wang S, Wei Y, Li Y, Qing H, Yan Y et al. (6 authors)", "query": "huntington neuroinflammation", "discovered": "2026-05-05T15:34:35.939440", "analysis": null }, "42035925": { "pmid": "42035925", "title": "Galectins as stress-integrating regulators of neuroimmune signaling and proteinopathy in the central nervous system.", "abstract": "Galectins are \u03b2-galactoside-binding lectins that play increasingly mechanistic functions in central nervous system (CNS) physiology and disease. Over the past decade, a rapidly expanding literature has identified galectins as regulators of microglial activation, misfolded protein pathology, vesicle damage sensing, autophagy, synaptic plasticity, myelination, vascular repair, and neuroimmune communication. Galectins operate across intracellular and extracellular compartments to integrate cellular", "journal": "Neurobiology of disease", "date": "2026 Apr", "authors": "Siew JJ, Chern Y", "query": "huntington neuroinflammation", "discovered": "2026-05-05T15:34:37.947228", "analysis": null }, "42057546": { "pmid": "42057546", "title": "mTOR Signalling in Neurodegenerative Disorders: Unveiling Key Factors, Mechanistic Insights, and Possible Therapeutic Interventions.", "abstract": "Neurodegenerative diseases (NDDs) are defined by the gradual degeneration of neuronal cells, wherein the accumulation of misfolded proteins can lead to memory impairments, motor dysfunctions, and other deteriorations. Despite the widespread impact, there are currently no viable pharmaceuticals to treat these disorders. The mTOR protein is a crucial regulator of cell survival, growth, autophagy, and apoptosis. Targeted modulation of mTOR signaling holds promise for mitigating neurodegeneration in", "journal": "Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology", "date": "2026 Apr", "authors": "Jha NK, Chauhan P, Abomughaid MM, Avinash D, Almutary AG et al. (13 authors)", "query": "huntington autophagy mTOR", "discovered": "2026-05-05T15:34:42.457821", "analysis": null }, "42716374": { "pmid": "42716374", "title": "Opto-CRISPR technologies in translational neuropharmacology.", "abstract": "Opto-CRISPR (optically controlled CRISPR/Cas) represents a major advancement in precision neurology by enabling localized gene editing within the nervous system at precise times and locations. While preclinical studies still rely largely on classical CRISPR/Cas systems, opto-CRISPR offers unprecedented opportunities to safely treat neurological diseases at their genetic roots. It achieves this by spatiotemporally correcting pathogenic mutations, halting toxic protein accumulation, repairing neur", "journal": "Neuropharmacology", "date": "2026 Sep", "authors": "Lau CH, Xia Q, Liang Q, Guo R, Zhu H", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:35:40.950860", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "41467429": { "pmid": "41467429", "title": "Therapeutic potential of astrocyte transdifferentiated neurons.", "abstract": "The permanent functional deficits resulting from the inability of adult mammalian central nervous system neurons to regenerate after injury present a significant clinical challenge. While traditional stem cell transplantation strategies continue to encounter ethical concerns and the risk of immune rejection, this impasse has shifted regenerative medicine research toward targeting endogenous astrocytes. Due to their intrinsic plasticity, widespread distribution throughout the central nervous syst", "journal": "Neural regeneration research", "date": "2026 Oct", "authors": "Liang X, Qin R, Qin Q, Xu W, Xu H et al. (12 authors)", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:35:40.950911", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42413168": { "pmid": "42413168", "title": "Huntington's disease in the era of somatic instability, biomarkers, and targeted therapies: A narrative review.", "abstract": "Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disorder caused by cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin gene (HTT), resulting in mutant huntingtin (mHTT) with toxic gain-of-function and partial loss of normal huntingtin function. This narrative review summarizes recent advances in genetics, pathophysiology, clinical features, diagnostic assessment, biomarkers, and therapeutic development. Genetic testing demonstrating an", "journal": "Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion", "date": "2026", "authors": "Cervantes-Arriaga A, Beltr\u00e1n-Torres AX, Romero-Garc\u00eda D, Rodr\u00edguez-Violante M", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:35:40.950921", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42360551": { "pmid": "42360551", "title": "Targeting mtDNA to Modulate Mitochondrial Dysfunction in Neurodegenerative Diseases.", "abstract": "Mitochondrial dysfunction is a common pathological feature of neurodegenerative diseases namely Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Although these disorders are primarily driven by disease-specific genetic and proteopathic mechanisms, increasing evidence suggests that secondary mitochondrial DNA (mtDNA) damage and heteroplasmy shifts may exacerbate bioenergetic failure and neuronal vulnerability. Distinguishing primary disease mechan", "journal": "Molecular neurobiology", "date": "2026 Jun", "authors": "Pramanik S, Debnath B, Chakraborty A, Islam A, Mullick S et al. (10 authors)", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:35:40.950927", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42827986": { "pmid": "42827986", "title": "A novel minimally humanized mouse model of aniridia for preclinical evaluation of CRISPR gene editing strategies.", "abstract": "Aniridia is a rare congenital vision-loss disorder primarily caused by variants in the paired box 6 (PAX6) gene. Current treatments do not maintain vision long term, nor address the underlying disease mechanism. CRISPR-mediated genome editing holds great promise for treating genetic diseases but requires demonstration of efficacy on human DNA to support translational relevance. The aim of this work was to generate and test a minimally humanized mouse model of aniridia, carrying a FLAG-tagged Pax", "journal": "Frontiers in genome editing", "date": "2026", "authors": "Mirjalili Mohanna SZ, Korecki AJ, Kazemian P, Lengyell TC, Adair BA et al. (7 authors)", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:35:40.950948", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42786474": { "pmid": "42786474", "title": "miR-196a reduces mutant Huntingtin aggregates by Rad23b-mediated degradation in Huntington's disease.", "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by abnormal expansions of poly-glutamine repeats in the mutant Huntingtin (mHTT). The expanded proteins form pathological aggregates to disrupt neuronal functions during disease progression, suggesting the clearance of the aggregates is considered as a potential direction for development of therapy. Our previous studies have demonstrated one specific microRNA, miR-196a, downregulates mHTT aggregates and improves the pathological ph", "journal": "Journal of biomedical science", "date": "2026 Sep", "authors": "Tung CW, Chan SC, Chen YC, Wu PM, Cheng PH et al. (7 authors)", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:35:40.950953", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42642835": { "pmid": "42642835", "title": "Unraveling Neurodegeneration: Common Molecular Mechanisms and Novel Therapeutic Concepts in Major Neurodegenerative Disorders.", "abstract": "Although Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Huntington's disease (HD) present with markedly different clinical phenotypes, these neurodegenerative diseases (NDDs) appear to converge on a shared set of underlying molecular disturbances. This review sought to integrate disease-specific causative triggers with shared pathogenic pathways, focusing on neuroinflammatory signaling, oxidative imbalance, mitochondrial impa", "journal": "Brain and behavior", "date": "2026 Aug", "authors": "Aldaghi FS, Siahpoosh Z, Salehi Z, Mashayekhi F, Sohrabnezhad S", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:35:40.950959", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "41570009": { "pmid": "41570009", "title": "Silencing of human HTT by targeted CRISPR/dCas9-mediated epigenetic editing.", "abstract": "BackgroundGene silencing is widely recognized as a promising therapeutic approach for dominant monogenic disorders. Current silencing strategies, many of which are transient, utilize RNA interference. Gene silencing may also be achieved through directed epigenetic editing using a CRISPR/dCas9 effector fused to DNA methyltransferase 3A (dCas9-DNMT3A). We used this system to direct DNA methylation to HTT, the causal gene underlying the autosomal dominant neurodegenerative disorder Huntington's dis", "journal": "Journal of Huntington's disease", "date": "2026 Aug", "authors": "Tay YL, Thomson SB, Hnatova S, Ng S, Teo SR et al. (14 authors)", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:35:40.950964", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42400823": { "pmid": "42400823", "title": "Update on Genetic Chorea.", "abstract": "Chorea is a symptom of numerous pathophysiologically and clinically heterogeneous genetic conditions. A number of developments have been made in this field over the last years linked to improved genomic testing, large cohort collaborations and improved understanding of the molecular mechanisms. This review aims to provide an update on the new genetic conditions and phenotypes linked to chorea disorders, their modification factors and pathophysiological background. Several novel genetic condition", "journal": "Current neurology and neuroscience reports", "date": "2026 Jul", "authors": "Ostrozovicova M, Skorvanek M", "query": "huntington somatic expansion CAG", "discovered": "2026-10-04T17:35:44.360847", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42210302": { "pmid": "42210302", "title": "Temporal single-cell atlas of full-length Huntington's disease mouse model defines stage-specific signatures of corticostriatal dysfunction.", "abstract": "Huntington's disease (HD) involves progressive corticostriatal dysfunction, yet the temporal dynamics and cell type-specific vulnerability patterns remain incompletely understood. While recent single-cell studies in rapidly progressing models have revealed early developmental and regional changes, temporal profiling distinguishing pathogenic mechanisms from normal aging in full-length HTT models remains lacking. Resolving stage-specific temporal dynamics across interconnected striatal and cortic", "journal": "Molecular neurodegeneration", "date": "2026 May", "authors": "Robbins AB, Ranum PT, Huerta-Ocampo I, Kuckyr M, Davidson BL", "query": "huntington somatic expansion CAG", "discovered": "2026-10-04T17:35:44.360887", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42549268": { "pmid": "42549268", "title": "Enhancing the detection of HTT1a with neoepitope antibodies in mouse models of Huntington's disease.", "abstract": "Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the huntingtin (HTT) gene, encoding an expanded polyglutamine tract in the huntingtin (HTT) protein. The pathogenic CAG repeat of HTT is unstable and undergoes progressive somatic expansion in specific brain cells and peripheral tissues throughout life. Genes involved in DNA mismatch repair pathways, which promote repeat expansion, have been identified as genetic modifiers of the disease", "journal": "Brain communications", "date": "2026", "authors": "Osborne GF, Smith EJ, Sathasivam K, Kang Z, Nita IM et al. (9 authors)", "query": "huntington somatic expansion CAG", "discovered": "2026-10-04T17:35:44.360895", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42619717": { "pmid": "42619717", "title": "Targeted quantification assays for DNA repair and handling proteins and interactions in Huntington's disease models.", "abstract": "Huntington's disease (HD) is a life-altering genetic neurodegenerative disorder, with cognitive, motor, and psycho-social effects that have consequential impacts on the individuals and their families. While current treatments improve disease symptoms, there are no FDA-approved therapies that prevent disease progression. Converging lines of evidence from human GWAS and mouse models point to DNA repair and handling (R/H) proteins as promising therapeutic targets due to their ability to modulate so", "journal": "bioRxiv : the preprint server for biology", "date": "2026 Jul", "authors": "Greco TM, Hutton JE, Justice JL, Reed TJ, Vogt TF et al. (7 authors)", "query": "huntington somatic expansion CAG", "discovered": "2026-10-04T17:35:44.360902", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42436050": { "pmid": "42436050", "title": "Targeting DNA mismatch repair in Huntington's disease.", "abstract": "Somatic expansion of the HTT CAG repeat is a key feature of Huntington's disease (HD) pathogenesis. Mismatch repair (MMR) enzymes drive this process through erroneous DNA repair, with variants in MMR genes modifying the onset and progression of disease features. Cell-type-specific CAG repeat sizing recently confirmed that elevated somatic expansion underlies the selective vulnerability of HD medium spiny neurons, with expansion beyond certain CAG thresholds associated with distinct stages of cel", "journal": "Trends in neurosciences", "date": "2026 Sep", "authors": "Bunting EL, Panhale A, McColgan P, Koi M, Brundin P et al. (6 authors)", "query": "huntington somatic expansion CAG", "discovered": "2026-10-04T17:35:44.360909", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42327018": { "pmid": "42327018", "title": "Somatic CRISPR editing of Msh3 mitigates Huntington's disease pathology in mice.", "abstract": "Huntington's disease (HD) is a fatal, dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in Huntingtin ( HTT ) exon 1. Further progressive CAG repeat expansion occurs in somatic cells, particularly in neurons, and drives the timing of clinical onset. Therefore, therapeutic strategies to slow somatic expansion are predicted to be disease-modifying. Somatic CAG expansion is driven by mismatch repair protein MSH3, a leading therapeutic target supported by human genetic", "journal": "bioRxiv : the preprint server for biology", "date": "2026 Jun", "authors": "Oliver E, Kovalenko M, Lou\u00e7\u00e3 M, Jiang A, Westerdahl J et al. (15 authors)", "query": "huntington somatic expansion CAG", "discovered": "2026-10-04T17:35:44.360916", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42182232": { "pmid": "42182232", "title": "C57BL/6 BAC-CAG Huntington's disease mice show somatic CAG expansion and responses to small interfering RNAs comparable to the FVB strain.", "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by CAG repeat expansion in the huntingtin (HTT) gene, with longer repeats linked to earlier onset. Somatic CAG expansion, particularly in the striatum, contributes to disease progression and is influenced by HTT biology and genetic modifiers. Modulating somatic expansion is emerging as a promising approach to slow or prevent HD, and mouse models have been crucial for preclinical testing of different therapeutic strategies. The BAC-", "journal": "bioRxiv : the preprint server for biology", "date": "2026 May", "authors": "Belgrad J, Summers A, Hildebrand S, Sapp E, Luu E et al. (13 authors)", "query": "huntington somatic expansion CAG", "discovered": "2026-10-04T17:35:44.360936", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "40808412": { "pmid": "40808412", "title": "cGAS-STING axis: A central regulator of neural homeostasis and neuroinflammatory pathogenesis.", "abstract": "An increasing amount of evidence shows that type I interferon response, which is induced by cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) and stimulator of interferon genes (STING) is closely associated with health and neuroinflammatory diseases. Abnormal activation or loss of control of the cGAS-STING axis affects the development of neuroinflammation. Thus, we examined its role in major neurological diseases, including traumatic brain injury, Alzheimer's disease, Parkin", "journal": "Neural regeneration research", "date": "2026 Aug", "authors": "Zhang J, Li J, Li Y, Liu C, Shi L et al. (8 authors)", "query": "huntington drug repurposing", "discovered": "2026-10-04T17:35:47.632096", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42161225": { "pmid": "42161225", "title": "Bumetanide as a potential treatment for neurodegenerative and neurodevelopmental disorders: A systematic review.", "abstract": "Neurological disorders represent a major global health burden, affecting an estimated 3.4 billion individuals worldwide. Bumetanide, a clinically approved loop-diuretic and antagonist of the Na+ -K+-Cl- cotransporter NKCC1, has recently emerged as a candidate for repurposing in the treatment of neurological disorders. Disrupted excitation-inhibition balance, driven in part by depolarizing GABAA receptor signaling resulting from altered chloride homeostasis, has been implicated across multiple ne", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "date": "2026 Jul", "authors": "McNamara O, Delany T, Kwakowsky A", "query": "huntington drug repurposing", "discovered": "2026-10-04T17:35:47.632143", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42311464": { "pmid": "42311464", "title": "GLP-1 Receptor Agonists in Neurological Disorders: From Mechanisms to Clinical Translation.", "abstract": "Glucagon-like peptide-1 receptor agonists, or GLP-1RAs, have been used for years to treat type 2 diabetes and obesity. More recently, it has become clear that these receptors are widely distributed throughout the central nervous system (CNS), which has raised the possibility of repurposing these drugs for neurological disorders. In this review we go through the evidence across a range of neurological conditions, discuss the main mechanisms thought to explain their neuroprotective effects, and po", "journal": "Drug design, development and therapy", "date": "2026", "authors": "Li P, Gao Y, Liu W", "query": "huntington drug repurposing", "discovered": "2026-10-04T17:35:47.632151", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42474536": { "pmid": "42474536", "title": "From glycemic control to neuroprotection: alogliptin as a repurposed candidate for Huntington's disease.", "abstract": "Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and psychiatric disturbances, for which no disease-modifying therapies are currently available. Emerging evidence implicates metabolic impairment, mitochondrial dysfunction, oxidative stress, and neuroinflammation as central contributors to HD pathogenesis, thereby highlighting novel avenues for therapeutic intervention beyond conventional strategies. I", "journal": "Metabolic brain disease", "date": "2026 Jul", "authors": "Choudhary G, Vashisht K, Sharma V, Ashawat MS, Kushawaha SK", "query": "huntington drug repurposing", "discovered": "2026-10-04T17:35:47.632158", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "41578740": { "pmid": "41578740", "title": "Targeting UCHL3 attenuates pathological markers in neuronal models of Huntington's disease.", "abstract": "Huntington's disease is an autosomal dominant neurodegenerative disease with a well-characterized genetic aetiology of a CAG expansion mutation in the huntingtin (HTT) gene, yet it remains without a cure. The hallmark of Huntington's disease is the accumulation of intraneuronal aggregates of mutant HTT protein and polyglutamine (polyQ)-containing fragments, which causes impaired proteostasis and is an important Huntington's disease therapeutic target. Aggregate-prone protein clearance primarily ", "journal": "Brain : a journal of neurology", "date": "2026 Jun", "authors": "Ishtayeh H, Battistoni E, Pochtar S, McHugh TLM, Tshilenge KT et al. (12 authors)", "query": "huntington drug repurposing", "discovered": "2026-10-04T17:35:47.632180", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42432671": { "pmid": "42432671", "title": "The role of AI-assisted drug repurposing in neurological disorders: a systematic review of validation strategies, challenges and opportunities.", "abstract": "Neurological disorders refer to a diverse group of conditions that affect the brain, peripheral nerves, and spinal cord and impair socioemotional, cognitive, motor, and sensory functions. Alzheimer's disease (AD), Multiple Sclerosis (MS), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are some of the well-known neurodegenerative diseases that affect millions of people worldwide. Despite the advanced technologies and nano-drug delivery systems, the su", "journal": "Journal of nanobiotechnology", "date": "2026 Jul", "authors": "Chen F, Wang L, Liu H, Khan Q, Tang B et al. (6 authors)", "query": "huntington drug repurposing", "discovered": "2026-10-04T17:35:47.632187", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42274555": { "pmid": "42274555", "title": "Polypharmacology of Pathway Crosstalk in Neurodegenerative Diseases: Chemical Modulation of Interconnected Signaling Networks.", "abstract": "Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), arise from highly interconnected molecular and cellular abnormalities that progressively lead to neuronal dysfunction, synaptic failure, and cell death. This review provides a unified framework to understand the interrelated molecular mechanisms driving these diseases, with a focus on identifying key disease-specific intervention nodes. Co", "journal": "Cells", "date": "2026 May", "authors": "Khan MS, Zafar I, Noman M, Yang G, Kang KS et al. (6 authors)", "query": "huntington drug repurposing", "discovered": "2026-10-04T17:35:47.632192", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42372889": { "pmid": "42372889", "title": "Deciphering the interaction of tetrabenazine with lactoferrin: Insights from molecular dynamics and multi-spectroscopic approaches.", "abstract": "Lactoferrin (LTF) is an iron-binding glycoprotein that has gained increasing attention in therapeutics for neurodegenerative diseases worldwide. This can be owed to its ability to cross the blood-brain barrier and modulate oxidative stress and inflammation. The present study explores the interaction of tetrabenazine (TBZ), an FDA-approved drug for Huntington's disease, with LTF using an integrated computational and experimental approach. The results from molecular docking analysis demonstrated t", "journal": "International journal of biological macromolecules", "date": "2026 Sep", "authors": "Dinislam K, Alenad A, Zuberi A, Khan MS", "query": "huntington drug repurposing", "discovered": "2026-10-04T17:35:47.632196", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42435587": { "pmid": "42435587", "title": "Precision therapeutics and innovative clinical trial design in neurodegenerative diseases.", "abstract": "Neurodegenerative diseases are biologically heterogeneous disorders characterized by progressive neuronal dysfunction, overlapping molecular pathologies, and limited disease-modifying therapies. Advances in biomarker development, molecular staging, and precision medicine are reshaping therapeutic strategies and clinical trial design across Parkinson's disease, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington's disease, and related disorders. This review sum", "journal": "Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion", "date": "2026", "authors": "Dom\u00ednguez-Garc\u00eda A, Delgado-Uriarte JC, Cervantes-Arriaga A", "query": "huntington biomarker neurofilament", "discovered": "2026-10-04T17:35:50.846440", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42512450": { "pmid": "42512450", "title": "Molecular Mechanisms of Neurodegenerative Diseases: Emerging Biomarkers and Therapeutic Targets.", "abstract": "Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), involve the gradual loss of structure or function of neurons in the nervous system and are an increasing threat to the aging population worldwide. Although these disorders have different clinical features which affect cognition, movement and other vital body functions, they share key underlying molecular and cellular processes. This sta", "journal": "Brain sciences", "date": "2026 Jun", "authors": "Yogi S, Singh A", "query": "huntington biomarker neurofilament", "discovered": "2026-10-04T17:35:50.846483", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42782432": { "pmid": "42782432", "title": "Fluid and Imaging Biomarkers in Huntington's Disease.", "abstract": "Growing interest in earlier and mechanism-targeted interventions for Huntington's disease (HD) has brought focus on biomarkers capable of informing trial design and regulatory pathways. This review discusses recent advances in fluid and neuroimaging biomarkers since the introduction of the HD-Integrated Staging System (HD-ISS), focusing on candidates with the most relevant evidence for regulatory applications. Neurofilament light (NfL) has become a versatile biomarker for prognostic enrichment a", "journal": "Current neurology and neuroscience reports", "date": "2026 Sep", "authors": "Broom EL, Hanson-Baiden J, Byrne LM", "query": "huntington biomarker neurofilament", "discovered": "2026-10-04T17:35:50.846491", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42607284": { "pmid": "42607284", "title": "CSF Leukocytes Transiently Increase Before Onset of Huntington Disease in Association With a Stage-Specific CSF Cytokine/Chemokine Pattern.", "abstract": "CSF inflammatory biomarkers in Huntington disease (HD), a neurodegenerative CAG-triplet expansion disorder, usually increase with disease progression. CSF leukocytes as an inflammatory marker have not been explored in HD. We explored high-precision CSF-leukocyte counts across different HD stages in the multicenter prospective biosample HD study HDClarity and their association with CSF neurofilament light chain (NFL) and cytokine and chemokine patterns. A cross-sectional case-control study of the", "journal": "Neurology(R) neuroimmunology & neuroinflammation", "date": "2026 Sep", "authors": "Gao Y, \u00c1sbj\u00f6rnsd\u00f3ttir B, Vinther-Jensen T, Von Essen MR, Hellem MNN et al. (11 authors)", "query": "huntington biomarker neurofilament", "discovered": "2026-10-04T17:35:50.846601", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42413317": { "pmid": "42413317", "title": "Effects of physical exercise on neurofilament light chain in multiple sclerosis and other neurological disorders: A systematic review.", "abstract": "Neurofilament light chain (NfL) is a well-established biomarker of axonal damage and neurodegeneration, with critical relevance in multiple sclerosis (MS) and other neurological disorders. This systematic review primarily aims to assess the impact of physical exercise on circulating NfL concentrations in people with MS, while secondarily exploring its effects across other neurological conditions. Five databases (PubMed, Scopus, Web of Science, EBSCO, and Cochrane) were searched according to PRIS", "journal": "Multiple sclerosis and related disorders", "date": "2026 Sep", "authors": "De Le\u00f3n-Mu\u00f1oz A, Rubio-Arias J\u00c1, \u00c1vila-Gand\u00eda V, Andreu-Caravaca L", "query": "huntington biomarker neurofilament", "discovered": "2026-10-04T17:35:50.846609", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42527584": { "pmid": "42527584", "title": "In vivo CRISPR base editing for treatment of Huntington's disease.", "abstract": "Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat within exon 1 of the huntingtin (HTT) gene, resulting in a mutant protein that drives neuronal dysfunction and loss. A key event in the pathogenesis of HD is proteolytic cleavage of mutant HTT, which generates aggregation-prone N-terminal fragments that contribute to toxicity. Strategies that prevent this process thus hold therapeutic potential. Here we develop CRISPR base editors that generate prote", "journal": "Nature biomedical engineering", "date": "2026 Jul", "authors": "Shirguppe S, Gapinske M, Swami D, Shenouda K, Miskalis A et al. (25 authors)", "query": "huntington CRISPR", "discovered": "2026-10-04T17:35:54.187191", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42439976": { "pmid": "42439976", "title": "CRISPR-Cas9-based therapies for Huntington's disease and Friedreich's ataxia: mechanisms, advances, and future perspectives.", "abstract": "Huntington's disease (HD) and Friedreich's ataxia (FRDA) are progressive inherited neurodegenerative disorders caused by trinucleotide repeat expansions but characterized by distinct pathogenic mechanisms. HD arises from a coding-region CAG expansion in the HTT gene that produces toxic gain-of-function effects of mutant huntingtin (mHTT), whereas FRDA results primarily from intronic GAA repeat expansion in FXN, leading to epigenetic repression and frataxin deficiency. The emergence of CRISPR-bas", "journal": "Neurogenetics", "date": "2026 Jul", "authors": "Mundada AR, Badikol AR, Mangu K", "query": "huntington CRISPR", "discovered": "2026-10-04T17:35:54.187225", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42427629": { "pmid": "42427629", "title": "iPSC Neurodegenerative Disease Initiative isogenic CAG repeat iPSC line for Huntington's disease.", "abstract": "The generation of iPSC lines expressing 21, 56 and 79 glutamine repeats within the HTT protein and homozygous KO of HTT in the KOLF2.1J background as an additional disease series within the iPSC Neurodegenerative Disease Initiative (iNDI) collection. All iPSCs, even those expressing long repeats of 79Q or HTT KO, were capable of differentiating to striatal and cortical neurons, astrocytes and microglia using established protocols. General quality control stains and morphological analyses are des", "journal": "bioRxiv : the preprint server for biology", "date": "2026 Jul", "authors": "Salazar L, Burns MS, Stocksdale JT, Wang KQ, Cao G et al. (14 authors)", "query": "huntington CRISPR", "discovered": "2026-10-04T17:35:54.187235", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42576574": { "pmid": "42576574", "title": "Emerging Pharmacological Therapies for Huntington's Disease: Translational Insights from Recent Clinical Trials.", "abstract": "Huntington's disease [HD] is a progressive, autosomal dominant neurodegenerative disorder caused by a pathogenic CAG repeat expansion in the HTT gene, resulting in mutant huntingtin [mHTT] protein accumulation, neuronal dysfunction, and selective neurodegeneration. Current pharmacological management remains largely symptomatic, with no approved therapies capable of modifying disease progression. In recent years, however, significant advances in molecular neuroscience and translational medicine h", "journal": "Current pharmaceutical biotechnology", "date": "2026 Jul", "authors": "Semwal BC, Singh K, Sharma R, Sharma D, Sharma A et al. (7 authors)", "query": "huntington CRISPR", "discovered": "2026-10-04T17:35:54.187241", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42265016": { "pmid": "42265016", "title": "Which HTT transcript to lower?", "abstract": "Huntington's disease (HD) RNA therapeutics have focused on lowering canonical huntingtin (HTT), yet clinical benefit remains uncertain. Papadopoulou et al. and Bragg et al. suggest that HTT1a-engaging strategies can produce stronger molecular rescue than full-length HTT lowering that spares HTT1a, highlighting transcript-species coverage as a key variable in HTT-lowering pharmacology.", "journal": "Trends in pharmacological sciences", "date": "2026 Jul", "authors": "Zhang M", "query": "huntington antisense oligonucleotide", "discovered": "2026-10-04T17:35:57.204763", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "41467439": { "pmid": "41467439", "title": "Microbiota-gut-brain axis and bile acids-driven neuromodulation.", "abstract": "Bile acids emerge as multifunctional signaling molecules with dual hepatic and microbial origins, acting through farnesoid X receptor and Takeda G protein-coupled receptor 5 to influence inflammation and metabolism. Their dysregulation is consistently observed across various neurodegenerative diseases. The microbiota-gut-brain axis is a pivotal conduit for bile acids-driven neuromodulation, while sex-specific bile acid profiles and signaling pathways introduce critical biological heterogeneity. ", "journal": "Neural regeneration research", "date": "2026 Sep", "authors": "Dong T, Zhang T, Wang H, Zhang J, Abdullah R et al. (7 authors)", "query": "huntington neuroinflammation", "discovered": "2026-10-04T17:36:00.551010", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "40808411": { "pmid": "40808411", "title": "Metallothionein and neurodegenerative diseases.", "abstract": "Neurodegenerative diseases, which mainly include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, and Huntington's disease, are a group of disorders characterized by loss of neurons in the brain and spinal cord. However, the underlying pathogenetic mechanisms of these disorders remain unclear. The metal ion hypothesis is considered a possible cause of a variety of neurodegenerative diseases. This hypothesis posits that the homeostatic imbalance of metal ", "journal": "Neural regeneration research", "date": "2026 Aug", "authors": "Cheng Y, Zhao Y, Chen C, Zhang F", "query": "huntington neuroinflammation", "discovered": "2026-10-04T17:36:00.551061", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42135109": { "pmid": "42135109", "title": "Epigenetic noise in the aging brain: tuning neuronal vulnerability to neurodegeneration.", "abstract": "Aging is the predominant risk factor for neurodegenerative diseases, yet the mechanisms linking biological aging to selective neuronal degeneration remain incompletely understood. Accumulating evidence indicates that aging progressively disrupts epigenetic regulation, manifested as increased epigenetic noise in DNA methylation, histone modifications, and chromatin accessibility, which undermines transcriptional precision and the stability of neuronal identity. Recent advances in single-cell and ", "journal": "Trends in neurosciences", "date": "2026 Jun", "authors": "Yin X, Zhang H, Zhang R, Xue J, Hou Y", "query": "huntington neuroinflammation", "discovered": "2026-10-04T17:36:00.551070", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42697520": { "pmid": "42697520", "title": "Microbiota-derived metabolite-GPCR signalling in neurodegeneration.", "abstract": "The gut microbiome acts as a primary regulator of host homeostasis, influencing the entire body through bidirectional communication along the gut-brain axis (GBA). Dysbiosis, which is defined as a state of microbial imbalance involving alterations in community composition and function, can disrupt the synthesis of important microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), bile acids and neurotransmitter precursors. This can lead to impaired essential host signalling pathw", "journal": "Neuroscience", "date": "2026 Nov", "authors": "Sharma A, Jatana N", "query": "huntington neuroinflammation", "discovered": "2026-10-04T17:36:00.551080", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "41467421": { "pmid": "41467421", "title": "Cell-based immunotherapy for neurodegenerative disease: A promising avenue.", "abstract": "Neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disease are characterized by progressive neuronal loss and chronic neuroinflammation, with current treatments remaining largely symptomatic. This review explores the potential of cell-based immunotherapy as a disease-modifying strategy. Advances in stem cell biology and immune engineering have facilitated the development of therapies using mesenchymal stem cells, chimeric ", "journal": "Neural regeneration research", "date": "2026 Oct", "authors": "Huerta TJ, Urbina-Mu\u00f1oz V, Urra-Alvarez V, Villablanca C, Gomez-Perez LS et al. (8 authors)", "query": "huntington neuroinflammation", "discovered": "2026-10-04T17:36:00.551087", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42598675": { "pmid": "42598675", "title": "Tracing neuroinflammation in neurodegeneration: insights from a scoping review on biofluid biomarkers.", "abstract": "Neuroinflammation is increasingly recognized as a key pathological process in neurodegenerative disease and can be monitored using biofluid biomarkers. Objective biomarkers may aid diagnosis, prognosis and progression. We conducted a scoping review of neuroinflammation biomarkers across major neurodegenerative diseases covering the past 23 years, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington's disease, Lewy body dementia, m", "journal": "Brain communications", "date": "2026", "authors": "van de Zande NA, Ruiter CCC, Polman MA, Brama SCM, Roos RAC et al. (7 authors)", "query": "huntington neuroinflammation", "discovered": "2026-10-04T17:36:00.551095", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42383392": { "pmid": "42383392", "title": "Role of Toll-like receptors and oral-gut-brain axis in neurodegenerative and neuropsychiatric disorders.", "abstract": "The oral-gut-brain axis is a path connecting the gastrointestinal tract and the central nervous system (CNS). The gut microbiota influences the immune system, metabolism, and nerve cells through the production of neurotransmitters and microbial metabolites that can cross the blood-brain barrier (BBB). The interplay between neuroinflammation and altered oral and gut microbiota is a bidirectional complex path modulated by inflammatory mediators. Recent studies suggest a potential role for Toll-lik", "journal": "Reviews in the neurosciences", "date": "2026 Jul", "authors": "Sabouri E, Shahmoradi T, Keshvari NZ, Khodaee P, Saleki K et al. (6 authors)", "query": "huntington neuroinflammation", "discovered": "2026-10-04T17:36:00.551125", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42087813": { "pmid": "42087813", "title": "Neuroinflammation and neurodegeneration trigger a specific splice form of ribosomal protein S24.", "abstract": "Neuroinflammation, particularly that involving reactive microglia, the brain's resident immune cells, is implicated in the pathogenesis of major neurodegenerative diseases (NDs). Multiple studies have reported changes in ribosomal protein (RP) expression during neurodegeneration, but the significance of these changes remains unclear. Ribosomes are evolutionarily conserved protein-synthesizing machines, and although commonly viewed as invariant, accumulating evidence suggests functional ribosome ", "journal": "Brain : a journal of neurology", "date": "2026 May", "authors": "Magadi SS, Jonson M, Lucena PB, Caliandro MF, Almeida B et al. (23 authors)", "query": "huntington neuroinflammation", "discovered": "2026-10-04T17:36:00.551134", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42817119": { "pmid": "42817119", "title": "Neuroinflammation and Autophagy in Neurodegeneration: Cellular Mechanisms and Therapeutic Strategies.", "abstract": "Neurodegenerative diseases, including Huntington's disease, Parkinson's disease, Alzheimer's disease, and Amyotrophic Lateral Sclerosis (ALS), are characterized by progressive neuronal dysfunction and loss, often accompanied by toxic protein aggregation and chronic neuroinflammation. Increasing evidence indicates that dysregulated autophagy and persistent inflammatory responses are central drivers of disease onset and progression. Autophagy, a fundamental cellular degradation and recycling proce", "journal": "CNS & neurological disorders drug targets", "date": "2026 Sep", "authors": "Verma A, Kushwaha SKS, Kushwaha N, Dutta S, Nigam P", "query": "huntington autophagy mTOR", "discovered": "2026-10-04T17:36:03.807317", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42476327": { "pmid": "42476327", "title": "Exploring shared genetic pathways and gene interplay in major neurodegenerative diseases: a comprehensive review.", "abstract": "Neurodegenerative diseases are progressive disorders that involve the loss and dysfunction of neurons. Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, Frontotemporal dementia are examples of diseases. While different clinically, these disorders have a common genetic, molecular and cellular basis. This review examines the common genetic pathways, along with the interactions between genes of major neurodegenerative diseases, with a focus on the key ge", "journal": "Gene", "date": "2026 Nov", "authors": "Pattnaik PP, Prusty SK, Pati S, Jew KA, Bora AK et al. (7 authors)", "query": "huntington autophagy mTOR", "discovered": "2026-10-04T17:36:03.807354", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42560011": { "pmid": "42560011", "title": "Molecular switches of SQSTM1: the impact of post-translational modifications on autophagy and neurodegeneration.", "abstract": "SQSTM1/p62 (sequestosome 1) is an important receptor protein involved in many cellular signaling processes, including macroautophagy/autophagy. It is a molecular hub for cellular homeostasis and cellular responses. Within autophagy, SQSTM1 targets ubiquitinated cargo for degradation, maintaining cellular proteostasis. Structurally, SQSTM1 consists of several domains that facilitate its binding to ubiquitinated cargo, the formation of SQSTM1 aggregate inclusions, interactions with MAP1LC3/LC3, an", "journal": "Autophagy", "date": "2026 Aug", "authors": "Abrar F, Martin DDO", "query": "huntington autophagy mTOR", "discovered": "2026-10-04T17:36:03.807360", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42814432": { "pmid": "42814432", "title": "Global, Regional, and National Burden of Heart Failure, 1990-2023: A Systematic Analysis for the Global Burden of Disease Study 2023.", "abstract": "Heart failure (HF) is a common condition with substantial geographical variation in its prevalence and underlying etiologies. Consistent and comparable data on the burden of HF within populations are needed to inform health system priorities. To estimate the global burden of HF. This cross-sectional study estimates disease burden using Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) methodologies to integrate multiple information sources. Data come from 204 countries and territ", "journal": "JAMA cardiology", "date": "2026 Sep", "authors": " , Johnson CO, Abbasi M, Abbasifard M, Abbastabar H et al. (1142 authors)", "query": "huntington digital twin clinical trial", "discovered": "2026-10-04T17:36:07.076240", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "40903965": { "pmid": "40903965", "title": "Role of voltage-dependent anion channel 1 in neurodegeneration: Mechanisms, implications, and therapeutic potential.", "abstract": "Voltage-dependent anion channel 1 is an integral outer membrane protein of the mitochondria that governs apoptosis, enables metabolite exchange, and influences mitochondrial activity. In neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and Alzheimer's disease, oxidative stress, neuroinflammation, and mitochondrial dysfunction are frequent features. Voltage-dependent anion channel 1 is a key regulator of these processes. This review des", "journal": "Neural regeneration research", "date": "2026 Sep", "authors": "Parikh A, Cholavaram A, Chitti Babu AK, Deepankumar K, Vijayan M", "query": "huntingtin protein structure drug target", "discovered": "2026-10-04T17:36:10.265974", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42617409": { "pmid": "42617409", "title": "Current landscape and future perspectives of small-molecule therapeutics for Huntington's disease: From rational design to clinical translation.", "abstract": "Huntington's disease (HD) is a devastating neurodegenerative disorder characterized by the expansion of cytosine-adenine-guanine (CAG) repeats within the huntingtin (HTT) gene. Given their therapeutic potential, small-molecule strategies have gained significant traction, leading to the design of numerous lead candidates aimed at diverse pathological hallmarks of HD. These developmental efforts target various facets of the disease, including the inhibition and degradation of mutant huntingtin (mH", "journal": "European journal of medicinal chemistry", "date": "2026 Dec", "authors": "Jiang Y, Chen X, Xu Z, Chen X, Wang Q et al. (11 authors)", "query": "huntingtin protein structure drug target", "discovered": "2026-10-04T17:36:10.266030", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42679819": { "pmid": "42679819", "title": "Cross-species single-cell atlas of the striatum defines cell-type and subregion disease vulnerabilities.", "abstract": "The striatum is critical for decision-making, movement, and reward processing, functions achieved through subregional cellular and molecular specialization. Striatal cell types and subregions are differentially implicated in neurodegenerative and neuropsychiatric disorders, but the mechanisms underlying these vulnerabilities are poorly understood. Using single-nucleus RNA sequencing across 109 human and 22 mouse samples spanning dorsal and ventral striatum, we provide a comprehensive atlas of su", "journal": "Cell", "date": "2026 Oct", "authors": "Linville RM, James BT, Galani K, Ho LL, Shin JH et al. (29 authors)", "query": "huntington disease treatment", "discovered": "2026-10-04T17:36:32.079095", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42525403": { "pmid": "42525403", "title": "Global Burden of Elevated LDL-C: Findings From the Global Burden of Disease Study 2023.", "abstract": "Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C-related burden is critical for guiding prevention and treatment strategies. To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-dele", "journal": "JAMA", "date": "2026 Aug", "authors": " , Razo C, DeCleene NK, Johnson CO, Stark BA et al. (1225 authors)", "query": "huntington disease treatment", "discovered": "2026-10-04T17:36:32.079142", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42725013": { "pmid": "42725013", "title": "Treatment of Parkinson's Disease-Related Psychosis.", "abstract": "To provide an updated, clinically oriented overview of therapeutic strategies for Parkinson's disease-related psychosis (PDP), integrating current evidence on risk factors and available pharmacological and non-pharmacological treatments. This is a narrative, non-systematic review summarizing findings from targeted searches of PubMed, Embase, and Scopus, focusing on clinical trials, observational studies, consensus guidelines, and high-quality reviews addressing the epidemiology, pathophysiology,", "journal": "Clinical pharmacology : advances and applications", "date": "2026", "authors": "Rocha NP, Moreira Sassi KL, Furr Stimming E, Teixeira AL", "query": "huntington disease treatment", "discovered": "2026-10-04T17:36:32.079151", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42332177": { "pmid": "42332177", "title": "Trace Elements Dyshomeostasis and Toxic Metals Neurotoxicity in Neurodegenerative Diseases.", "abstract": "Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, are defined by the progressive loss of neurons through interconnected pathological mechanisms, including oxidative stress, mitochondrial dysfunction, protein aggregation, and neuroinflammation. Accumulating evidence implicates metal dyshomeostasis as a central and multifaceted contributor to these mechanisms, with roles ranging from a primary pathogenic driver in", "journal": "Biological trace element research", "date": "2026 Sep", "authors": "Tang M, Fleming E, Gu J, Shi H, Xu Y et al. (6 authors)", "query": "huntington disease treatment", "discovered": "2026-10-04T17:36:32.079156", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "41808287": { "pmid": "41808287", "title": "Five-Year Disease Progression in Synuclein Seeding Positive Sporadic Parkinson's Disease.", "abstract": "To provide a comprehensive description of disease progression in synuclein seeding assay (SAA) positive sporadic Parkinson Disease participants, using Neuronal Synuclein Disease integrated biological and functional impairment staging framework. We analyzed 5-year longitudinal data from 345 participants recruited in the Parkinson's Progression Markers Initiative with the diagnosis of early (less than 2\u2009years of clinical diagnosis at baseline and untreated) sporadic Parkinson's Disease, who were s", "journal": "Annals of clinical and translational neurology", "date": "2026 Sep", "authors": "Gonzalez-Latapi P, Gochanour C, Choi SH, Cho H, Caspell-Garcia C et al. (20 authors)", "query": "huntington disease treatment", "discovered": "2026-10-04T17:36:32.079587", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42276279": { "pmid": "42276279", "title": "Naringenin as a multi-target neuroprotective agent in neurodegenerative diseases.", "abstract": "Neurodegenerative diseases (ND) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS) are characterized by progressive neuronal loss driven by complex and multifactorial pathogenic mechanisms. Naringenin (NAR), a citrus-derived flavanone, has attracted considerable interest as a neuroprotective molecule due to its pleiotropic pharmacological activities such as antioxidant, anti-inflammatory and abil", "journal": "Neurochemistry international", "date": "2026 Sep", "authors": "Gurung N, Choi DY, Park PH", "query": "huntington disease treatment", "discovered": "2026-10-04T17:36:32.079594", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42156213": { "pmid": "42156213", "title": "Dysregulation of arginase and arginine pathways in neurodegenerative diseases: Metabolic and cellular dysfunction and therapeutic implications.", "abstract": "Neurodegenerative diseases are increasingly recognized as disorders associated with metabolic dysfunction with arginine metabolism emerging as a significant contributor. Arginase, by regulating the balance between arginine and ornithine, is positioned at the crossroads of multiple arginine metabolic pathways, thereby controlling a variety of cellular processes essential for proper brain homeostasis. Chronic disruption of these pathways may lead to dysfunction of neurons and glia ultimately resul", "journal": "Free radical biology & medicine", "date": "2026 Aug", "authors": "Nalepa M, Skweres A, W\u0119grzynowicz M", "query": "huntington disease treatment", "discovered": "2026-10-04T17:36:32.079599", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42625059": { "pmid": "42625059", "title": "Toward the clinical application of long-read sequencing in repeat-expansion disorders.", "abstract": "Repeat-expansion disorders (REDs) are a mechanistically and clinically well-defined subgroup of rare diseases caused by the expansion of short tandem repeats (STRs). These expansions can exceed several kilobases and show complex features, such as noncanonical secondary structures, somatic instability, repeat interruptions and allele-specific methylation. These characteristics are highly relevant for understanding disease mechanisms, clinical variability, prognosis and potentially therapeutic dec", "journal": "Nature genetics", "date": "2026 Sep", "authors": "Benarroch L, Pe\u0161ovi\u0107 J, Rossato M, Chen Z, Lucas MC et al. (37 authors)", "query": "huntington disease treatment", "discovered": "2026-10-04T17:36:32.079603", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42557400": { "pmid": "42557400", "title": "Subcutaneous Amivantamab and Lazertinib in PALOMA-3: Efficacy, Safety, and Administration: A Vodcast.", "abstract": "Intravenous (IV) amivantamab, an epidermal growth factor receptor (EGFR)-MET bispecific antibody, is approved for multiple indications alone or in combination for patients with EGFR-mutated advanced or metastatic nonsmall cell lung cancer (NSCLC). In the PALOMA-3 study, subcutaneous (SC) amivantamab was investigated to improve tolerability, reduce administration time, maintain efficacy, and improve patient experience. This vodcast reviews the rationale and data supporting SC amivantamab on the b", "journal": "Targeted oncology", "date": "2026 Sep", "authors": "Nguyen D", "query": "huntington disease treatment", "discovered": "2026-10-04T17:36:32.079606", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42600624": { "pmid": "42600624", "title": "Neurological effects of encapsulated dexamethasone sodium phosphate in children aged 6-9 years with ataxia telangiectasia (NEAT): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.", "abstract": "Ataxia telangiectasia is a rare, multisystem disorder with progressive cerebellar neurodegeneration and no approved treatments. The efficacy of corticosteroids, including erythrocyte encapsulated dexamethasone sodium phosphate (eDSP), which have been studied for two decades in this disease, has not yet been proven in randomised trials. We aimed to investigate the safety and efficacy of eDSP in children aged 6-9 years with ataxia telangiectasia. NEAT was a multicentre, randomised, double-blind, p", "journal": "The Lancet. Child & adolescent health", "date": "2026 Oct", "authors": "Russo S, Zielen S, Pietrucha B, Trischler J, Perlman S et al. (30 authors)", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:36:35.470479", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42801363": { "pmid": "42801363", "title": "Uncovering hidden protein networks in Huntington's disease: implications for pathogenesis and therapy.", "abstract": "Huntington's Disease is a neurodegenerative disorder that progresses over time and can be passed down from parent to child. In uncontrolled motor activities, behavioural problems come into play, as well as progressive mental decline. The CAG triplet in the HTT gene found on chromosome 4 undergoes changes, leading to the production of a mutant protein called huntingtin, which consists of a bigger-than-normal polyglutamine tract that then undergoes misfolding and produces toxic oligomers and fibri", "journal": "Molecular biology reports", "date": "2026 Sep", "authors": "Panwar C, Goel F, Garg VK", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:36:35.470520", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42149299": { "pmid": "42149299", "title": "Human iPSC\u2011based translational and reverse translational research for neurodegenerative diseases: emphasis on ALS and key advances.", "abstract": "Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD) cause progressive loss of specific neuronal populations and currently lack curative therapies. Animal models and immortalized cell lines incompletely recapitulate human pathology and genetic heterogeneity, limiting drug discovery. Human induced pluripotent stem cells (iPSCs) provide a patient\u2011specific platform for disease modelling, drug screeni", "journal": "Japanese journal of radiology", "date": "2026 Sep", "authors": "Morimoto S, Takahashi S, Okano H", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:36:35.470620", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42716230": { "pmid": "42716230", "title": "MicroRNAs in polyglutamine diseases: Mechanistic insights, circulating biomarkers, and emerging microRNA-based therapeutic strategies.", "abstract": "MicroRNAs (miRNAs) have emerged as critical regulators in the pathogenesis of polyglutamine (PolyQ) diseases-a group of fatal neurodegenerative disorders caused by CAG repeat expansions, such as Huntington's disease, spinocerebellar ataxias, dentatorubral-pallidoluysian atrophy, and spinal and bulbar muscular atrophy. This review synthesizes recent advances in miRNA dysregulation across all nine PolyQ diseases, focusing on studies published since 2019. We examine how specific miRNAs modulate cor", "journal": "Neurobiology of disease", "date": "2026 Oct", "authors": "Liu Y, Cui Y, Sun M, Gong L, Liu K et al. (8 authors)", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:36:35.470626", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42586226": { "pmid": "42586226", "title": "Cholesterol restores corticostriatal synaptic connectivity in Huntington's disease through BDNF/TrkB signalling, supporting a role for cholesterol pathways implicated by human genetic modifier studies.", "abstract": "Corticostriatal synaptic dysfunction is an early hallmark of Huntington's disease (HD), yet the mechanisms underlying synapse loss and its reversibility remain poorly understood. Brain cholesterol is essential for neuronal and synaptic function, and dysregulated cholesterol metabolism has emerged as a key feature of HD, with reduced cholesterol biosynthesis reported in rodent models and cholesterol replenishment shown to be beneficial. Consistent with these findings, GWAS identified HD modifier ", "journal": "Pharmacological research", "date": "2026 Sep", "authors": "Lenci A, Villa M, Scolz A, Birolini G, Conforti P et al. (18 authors)", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:36:35.470631", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42619255": { "pmid": "42619255", "title": "Mitochondria-Targeted Nanotherapies in Aging Neurodegenerative Disorders: Emerging Prospects and Clinical Potential.", "abstract": "Aging is a significant risk factor of neurodegenerative disorders (NDs) such as Huntington's, Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Although several clinical, neuroimaging, and biomarker-based diagnostic approaches are available for NDs, their limited sensitivity for early-stage detection, disease specificity, and prediction of disease progression continue to present significant clinical challenges, often resulting in delayed diagnosis and th", "journal": "Advanced healthcare materials", "date": "2026 Sep", "authors": "Gadhave DG, Jadhav AB, Waghamode NB, Khot S, Khan R et al. (9 authors)", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:36:35.470636", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42667453": { "pmid": "42667453", "title": "Ginsenosides: potential therapeutic implications in neurodegenerative diseases by inhibiting ferroptosis.", "abstract": "A positive correlation exists between the accelerating pace of population aging and the increasing prevalence of neurodegenerative diseases. Conditions such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) profoundly compromise patient quality of life, yet efficacious clinical interventions remain notably limited. The prevention and management of neurodegenerative diseases represent a critical global public health imperative. A comprehensive literatu", "journal": "Molecular biology reports", "date": "2026 Aug", "authors": "Liu C, Zhang Y", "query": "huntington disease gene therapy", "discovered": "2026-10-04T17:36:35.470640", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42644714": { "pmid": "42644714", "title": "Decoding neuronal vulnerability: Multidimensional analysis of D1R- and D2R- medium-sized spiny neurons in Huntington's disease.", "abstract": "Understanding the molecular mechanisms driving selective neuronal vulnerability to different neurodegenerative disorders remains a crucial, unsolved question. Here, we explored the case of Huntington's disease (HD), where the striatum and, specifically, dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) medium-sized spiny neurons (MSNs) exhibit differential susceptibility to the HTT CAG-repeat expansion mutation, with D2R-neurons being impacted earlier and more significantly. To unravel dif", "journal": "Brain pathology (Zurich, Switzerland)", "date": "2026 Nov", "authors": "Bergonzoni G, Pellegrini M, Savino A, Lazioli M, Geurs S et al. (23 authors)", "query": "huntington somatic expansion CAG", "discovered": "2026-10-04T17:36:38.527700", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42735686": { "pmid": "42735686", "title": "Loss of interruption in the HTT CAG repeat is associated with somatic expansion and loss of medium spiny neurons in Huntington's disease.", "abstract": "Synonymous loss-of-interruption variants in the expanded CAG repeat sequence of Huntingtin (HTT) accelerate the clinical onset and progression of Huntington's disease (HD). Medium spiny neurons (MSNs) are gradually lost in HD and undergo selective somatic CAG expansion, but it is unclear how somatic expansion relates to MSN pathology. Here, we show that MSNs with large (111-150 CAG) and very large (>150 CAG) somatic expansions are rare in early manifest HD but accumulate in proportion with durat", "journal": "Neuron", "date": "2026 Sep", "authors": "Kay C, Levesley J, M\u00e4tlik K, Findlay Black H, Harvey E et al. (19 authors)", "query": "huntington somatic expansion CAG", "discovered": "2026-10-04T17:36:38.527737", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42779800": { "pmid": "42779800", "title": "Chemically modified CRISPR enzymes for multi-organ genome editing in vivo.", "abstract": "Delivery remains the main obstacle to the development of in vivo genome editing therapies. CRISPR ribonucleoproteins confer high editing activity with transient exposure but lack intrinsic cell entry and targeting. Here we introduce PERCEPT, a delivery platform featuring reversible, covalent modification of CRISPR enzymes. PERCEPT enables modular installation of shielding polymers, amphiphilic delivery peptides and targeting ligands, allowing traceless cytosolic release of the native editor. A f", "journal": "bioRxiv : the preprint server for biology", "date": "2026 Sep", "authors": "Baehr CM, Ressnerova A, Kang M, Zhao S, Le B et al. (23 authors)", "query": "huntington CRISPR", "discovered": "2026-10-04T17:36:42.756628", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42581113": { "pmid": "42581113", "title": "Oxidative stress and inflammation in neurodegenerative disorders.", "abstract": "The brain's consumption of approximately 20% of the body's oxygen contributes to oxidative stress, a significant pathological factor in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. This oxidative stress, linked to low levels of antioxidant enzymes, drives neuronal death by facilitating membrane peroxidation of fatty acids, proteins, and DNA. Alzheimer's disease is characterized by amyloid-beta (A\u03b2) plaque ac", "journal": "Archives of toxicology", "date": "2026 Oct", "authors": "Jomova K, Alomar SY, Valko R, Nepovimova E, Kuca K et al. (6 authors)", "query": "huntington neuroinflammation", "discovered": "2026-10-04T17:36:46.676458", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42634335": { "pmid": "42634335", "title": "Metformin in Neurodegenerative Diseases: Mechanisms and Therapeutic Implications.", "abstract": "As the global burden of neurodegenerative disorders continues to rise with aging populations, there is growing interest in identifying widely available drugs that can be repurposed to target shared metabolic and inflammatory mechanisms underlying these conditions. Increasing evidence suggests that metabolic dysfunction, mitochondrial impairment, and chronic neuroinflammation play central roles in the pathogenesis of neurodegeneration, demonstrating the need for therapeutics that can modulate the", "journal": "Current neuropharmacology", "date": "2026 Aug", "authors": "Langmead AP, Keane BA, Jacob JA, Ramana KV", "query": "huntington neuroinflammation", "discovered": "2026-10-04T17:36:46.676500", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42770357": { "pmid": "42770357", "title": "Designing Multi-functional Antioxidants for Neurodegenerative Disorders.", "abstract": "Neurodegenerative disorders (NDs), including Alzheimer's disease, Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Huntington's disease (HD) and Multiple Sclerosis (MS), pose a major global health threat due to complex pathology, increased prevalence, and lack of effective therapies. Numerous findings have indicated that oxidative stress (OS) is a central and unifying pathological mechanism driving neuronal dysfunction and degeneration across these disorders. Excessive reactive oxy", "journal": "Mini reviews in medicinal chemistry", "date": "2026 Sep", "authors": "Sahu K, Sahu R, Mishra M, Chhabra N, Tiwari S et al. (9 authors)", "query": "huntington neuroinflammation", "discovered": "2026-10-04T17:36:46.676507", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } }, "42567782": { "pmid": "42567782", "title": "Interleukin-6 trans-signalling as a selectively targetable driver of neurodegeneration.", "abstract": "Interleukin-6 (IL-6) exerts protective and pathogenic effects in the central nervous system through distinct receptor-signalling modes. Classical signalling via membrane-bound IL-6 receptor (IL-6R) is often associated with homeostatic and reparative functions, whereas trans-signalling, mediated by soluble IL-6R, expands IL-6 responsiveness to gp130-expressing cells and may promote chronic inflammation. Emerging evidence implicates dysregulated IL-6 trans-signalling in amyotrophic lateral scleros", "journal": "Trends in neurosciences", "date": "2026 Sep", "authors": "Risby-Jones G, Lee JD, Fung JN", "query": "huntington neuroinflammation", "discovered": "2026-10-04T17:36:46.676513", "analysis": { "status": "not_analyzed", "reason": "discover-only scout; LLM analysis was not requested" } } }, "last_run": "2026-10-04T17:36:49.877464", "total_runs": 6, "last_lookback_days": 60, "last_mode": "discover_only" }