ArticleAnnals of neurology2018
Oligonucleotide therapy mitigates disease in spinocerebellar ataxia type 3 mice.
Article in Annals of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 2 of them syntheses that pooled it.
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Who cites it
97 citing papers in PubMed, 2 syntheses or guidelines pooled it, 154 citations in OpenAlex.
- Gene Suppression Therapies in Hereditary Cerebellar Ataxias: A Systematic Review of Animal Studies.Cells · 2023Pooled it
- The Efficacy and Safety of Transcranial Direct Current Stimulation for Cerebellar Ataxia: a Systematic Review and Meta-Analysis.Cerebellum (London, England) · 2021Pooled it
- Establishing Sensory Neurons as Therapeutic Targets in Peripheral Neuropathy Driven by Polyglutamine Expanded Murine ATXN3.Annals of neurology · 2026Article
- Experimental Models to Study Polyglutamine Spinocerebellar Ataxias: From Mechanisms to Therapeutic Developments.Cerebellum (London, England) · 2026Review
- An acyclic nucleic acid-modified siRNA targeting CAG expansions for polyglutamine disease treatment.Molecular therapy. Nucleic acids · 2026Article
- Beyond muscle: Delivering RNA therapeutics to the CNS in Duchenne muscular dystrophy.Journal of neuromuscular diseases · 2026Review
- Repeat-associated non-AUG translation as a common mechanism for the polyGln ataxias.Cell reports · 2026Article
- The Status and Future Directions of Treatments for Polyglutamine Spinocerebellar Ataxia: A Bibliometric and Visual Analysis.Current neuropharmacology · 2026Review
- Predicting disease progression in progressive cerebellar ataxias: integrating clinical, imaging, fluid, genetic, and digital biomarkers.Frontiers in neurology · 2026Review
- Ataxin-3 Overexpression via Adeno-associated Viral Vector Injection in the Primate Cerebellum: A Novel Model of Spinocerebellar Ataxia Type 3.Experimental neurobiology · 2025Article
- Comparison ofMolecular therapy. Nucleic acids · 2025Article
- Gene editing for Spinocerebellar ataxia type 3 taking advantage of the human ATXN3L paralog as replacement gene.Gene therapy · 2025Article
- Cerebellar lipid dysregulation in SCA3: A comparative study in patients and mice.Neurobiology of disease · 2025Article
- Early transcriptomic perturbations highlight the spinal cord as a key pathogenic region in spinocerebellar ataxia type 3.Frontiers in cellular neuroscience · 2025Article
- Regional distribution of polymorphisms associated to the disease-causing gene of spinocerebellar ataxia type 3.Journal of neurology · 2024Article
- Dysregulation of zebrin-II cell subtypes in the cerebellum is a shared feature across polyglutamine ataxia mouse models and patients.Science translational medicine · 2024Article
- Preferences for genetic interventions for SCA and Huntington's disease: results of a discrete choice experiment among patients.Orphanet journal of rare diseases · 2024Article
- Longitudinal Changes of Clinical, Imaging, and Fluid Biomarkers in Preataxic and Early Ataxic Spinocerebellar Ataxia Type 2 and 7 Carriers.Neurology · 2024Observational
- ASOs are an effective treatment for disease-associated oligodendrocyte signatures in premanifest and symptomatic SCA3 mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Glucocorticoid receptor-dependent therapeutic efficacy of tauroursodeoxycholic acid in preclinical models of spinocerebellar ataxia type 3.The Journal of clinical investigation · 2024Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveSpinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is the most common dominantly inherited ataxia. Despite advances in understanding this CAG repeat/polyglutamine expansion disease, there are still no therapies to alter its progressive fatal course. Here, we investigate whether an antisense oligonucleotide (ASO) targeting the SCA3 disease gene, ATXN3, can prevent molecular, neuropathological, electrophysiological, and behavioral features of the disease in a mouse model of SCA3.
methodsThe top ATXN3-targeting ASO from an in vivo screen was injected intracerebroventricularly into early symptomatic transgenic SCA3 mice that express the full human disease gene and recapitulate key disease features. Following a single ASO treatment at 8 weeks of age, mice were evaluated longitudinally for ATXN3 suppression and rescue of disease-associated pathological changes. Mice receiving an additional repeat injection at 21 weeks were evaluated longitudinally up to 29 weeks for motor performance.
resultsThe ATXN3-targeting ASO achieved sustained reduction of polyglutamine-expanded ATXN3 up to 8 weeks after treatment and prevented oligomeric and nuclear accumulation of ATXN3 up to at least 14 weeks after treatment. Longitudinal ASO therapy rescued motor impairment in SCA3 mice, and this rescue was associated with a recovery of defects in Purkinje neuron firing frequency and afterhyperpolarization.
interpretationThis preclinical study established efficacy of ATXN3-targeted ASOs as a disease-modifying therapeutic strategy for SCA3. These results support further efforts to develop ASOs for human clinical trials in this polyglutamine disease as well as in other dominantly inherited disorders caused by toxic gain of function. Ann Neurol 2018;83:64-77.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.