ArticleAnnals of neurology2016
RNAi prevents and reverses phenotypes induced by mutant human ataxin-1.
Article in Annals of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Gene Suppression Therapies in Hereditary Cerebellar Ataxias: A Systematic Review of Animal Studies.Cells · 2023Pooled it
- The ISG Atlas: a loss-of-function analysis characterizes antiviral properties of interferon stimulated genes.Nature communications · 2026Article
- Translational Relevance of SCA1 Models for the Development of Therapies for Spinocerebellar Ataxia Type 1.Biomedicines · 2025Review
- AAV-based delivery of RNAi targeting ataxin-2 improves survival and pathology in TDP-43 mice.Nature communications · 2025Article
- Fingolimod Prevents Neuroinflammation but Has a Limited Effect on the Development of Ataxia in a Mouse Model for SCA1.International journal of molecular sciences · 2025Article
- Current trends in gene therapy to treat inherited disorders of the brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Cas9 editing ofMolecular therapy. Nucleic acids · 2024Article
- Review
- The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects.Frontiers in immunology · 2024Review
- The potential value of disease-modifying therapy in patients with spinocerebellar ataxia type 1: an early health economic modeling study.Journal of neurology · 2023Article
- Review
- Therapeutic Strategies for Spinocerebellar Ataxia Type 1.Biomolecules · 2023Review
- Neuro-respiratory pathology in spinocerebellar ataxia.Journal of the neurological sciences · 2022Review
- Identification of the ataxin-1 interaction network and its impact on spinocerebellar ataxia type 1.Human genomics · 2022Article
- Combined overexpression of ATXN1L and mutant ATXN1 knockdown by AAV rescue motor phenotypes and gene signatures in SCA1 mice.Molecular therapy. Methods & clinical development · 2022Article
- Reduction of mutant ATXN1 rescues premature death in a conditional SCA1 mouse model.JCI insight · 2022Article
- Temporal Phenotypic Changes in Huntington's Disease Models for Preclinical Studies.Journal of Huntington's disease · 2022Article
- Lipid-based nanoparticles and RNA as innovative neuro-therapeutics.Frontiers in pharmacology · 2022Review
- Huntington's disease phenotypes are improved via mTORC1 modulation by small molecule therapy.PloS one · 2022Article
- Combinational treatments of RNA interference and extracellular vesicles in the spinocerebellar ataxia.Frontiers in molecular neuroscience · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveSpinocerebellar ataxia type 1 is an autosomal dominant fatal neurodegenerative disease caused by a polyglutamine expansion in the coding region of ATXN1. We showed previously that partial suppression of mutant ataxin-1 (ATXN1) expression, using virally expressed RNAi triggers, could prevent disease symptoms in a transgenic mouse model and a knockin mouse model of the disease, using a single dose of virus. Here, we set out to test whether RNAi triggers targeting ATXN1 could not only prevent, but also reverse disease readouts when delivered after symptom onset.
methodsWe administered recombinant adeno-associated virus (rAAV) expressing miS1, an artificial miRNA targeting human ATXN1 mRNA (rAAV.miS1), to a mouse model of spinocerebellar ataxia type 1 (SCA1; B05 mice). Viruses were delivered prior to or after symptom onset at multiple doses. Control B05 mice were treated with rAAVs expressing a control artificial miRNA, or with saline. Animal behavior, molecular phenotypes, neuropathology, and magnetic resonance spectroscopy were done on all groups, and data were compared to wild-type littermates.
resultsWe found that SCA1 phenotypes could be reversed by partial suppression of human mutant ATXN1 mRNA by rAAV.miS1 when delivered after symptom onset. We also identified the therapeutic range of rAAV.miS1 that could prevent or reverse disease readouts.
interpretationSCA1 disease may be reversible by RNAi therapy, and the doses required for advancing this therapy to humans are delineated. Ann Neurol 2016;80:754-765.
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