ArticleBrain : a journal of neurology2015
Broad distribution of ataxin 1 silencing in rhesus cerebella for spinocerebellar ataxia type 1 therapy.
Article in Brain : a journal of neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Gene Suppression Therapies in Hereditary Cerebellar Ataxias: A Systematic Review of Animal Studies.Cells · 2023Pooled it
- Translational Relevance of SCA1 Models for the Development of Therapies for Spinocerebellar Ataxia Type 1.Biomedicines · 2025Review
- Cell replacement in the degenerating cerebellum: a historical essay of discovery.Journal of neurology · 2025Review
- 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
- An update on mammalian and non-mammalian animal models for biomarker development in neurodegenerative disorders.Cellular and molecular life sciences : CMLS · 2025Review
- Review
- Therapeutic Strategies for Spinocerebellar Ataxia Type 1.Biomolecules · 2023Review
- 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
- New Perspectives of Gene Therapy on Polyglutamine Spinocerebellar Ataxias: From Molecular Targets to Novel Nanovectors.Pharmaceutics · 2021Review
- Current Status of Gene Therapy Research in Polyglutamine Spinocerebellar Ataxias.International journal of molecular sciences · 2021Review
- Design and Validation of a Multi-Point Injection Technology for MR-Guided Convection Enhanced Delivery in the Brain.Frontiers in medical technology · 2021Article
- Ophthalmic Manifestations and Genetics of the Polyglutamine Autosomal Dominant Spinocerebellar Ataxias: A Review.Frontiers in neuroscience · 2020Review
- Recent advances in molecular therapies for neurological disease: triplet repeat disorders.Human molecular genetics · 2019Review
- Targeted Oligonucleotides for Treating Neurodegenerative Tandem Repeat Diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Genetics, Mechanisms, and Therapeutic Progress in Polyglutamine Spinocerebellar Ataxias.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Article
- The long non-coding RNA NEAT1 is elevated in polyglutamine repeat expansion diseases and protects from disease gene-dependent toxicities.Human molecular genetics · 2018Article
- Article
- In Vivo Selection of a Computationally Designed SCHEMA AAV Library Yields a Novel Variant for Infection of Adult Neural Stem Cells in the SVZ.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Spinocerebellar ataxia type 1 is one of nine polyglutamine expansion diseases and is characterized by cerebellar ataxia and neuronal degeneration in the cerebellum and brainstem. Currently, there are no effective therapies for this disease. Previously, we have shown that RNA interference mediated silencing of ATXN1 mRNA provides therapeutic benefit in mouse models of the disease. Adeno-associated viral delivery of an engineered microRNA targeting ATXN1 to the cerebella of well-established mouse models improved motor phenotypes, neuropathy, and transcriptional changes. Here, we test the translatability of this approach in adult rhesus cerebella. Nine adult male and three adult female rhesus macaque were unilaterally injected with our therapeutic vector, a recombinant adeno-associated virus type 1 (rAAV1) expressing our RNAi trigger (miS1) and co-expressing enhanced green fluorescent protein (rAAV1.miS1eGFP) into the deep cerebellar nuclei using magnetic resonance imaging guided techniques combined with a Stealth Navigation system (Medtronics Inc.). Transduction was evident in the deep cerebellar nuclei, cerebellar Purkinje cells, the brainstem and the ventral lateral thalamus. Reduction of endogenous ATXN1 messenger RNA levels were ≥30% in the deep cerebellar nuclei, the cerebellar cortex, inferior olive, and thalamus relative to the uninjected hemisphere. There were no clinical complications, and quantitative and qualitative analyses suggest that this therapeutic intervention strategy and subsequent reduction of ATXN1 is well tolerated. Collectively the data illustrate the biodistribution and tolerability of rAAV1.miS1eGFP administration to the adult rhesus cerebellum and are supportive of clinical application for spinocerebellar ataxia type 1.
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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.