ArticleNature2017
Antisense oligonucleotide therapy for spinocerebellar ataxia type 2.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers, 2 of them syntheses that pooled it.
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Who cites it
183 citing papers in PubMed, 2 syntheses or guidelines pooled it, 321 citations in OpenAlex.
- Gene Suppression Therapies in Hereditary Cerebellar Ataxias: A Systematic Review of Animal Studies.Cells · 2023Pooled it
- Assisted delivery of antisense therapeutics in animal models of heritable neurodegenerative and neuromuscular disorders: a systematic review and meta-analysis.Scientific reports · 2018Pooled it
- Toward the clinical application of long-read sequencing in repeat-expansion disorders.Nature genetics · 2026Review
- Spinocerebellar Ataxia Type 12: Spectrums of Movement Disorders and Clinical Features.Neuro-degenerative diseases · 2026Review
- Pan-biological characteristics of ataxin-2 protein.Neural regeneration research · 2026Article
- A dish-to-biobank framework links β-cell nutrient-stress programs to genetic and dietary risk for Type 2 Diabetes.bioRxiv : the preprint server for biology · 2026Article
- A human Staufen1 BAC transgenic mouse exhibits abnormal autophagy and neurodegeneration across the central nervous system.Cell death & disease · 2026Article
- Therapeutic targeting of blood-derived protein infiltration to modulate neuroinflammation in cerebellar ataxia.Journal of neuroinflammation · 2026Article
- Diagnostic Yield of Comprehensive Reanalysis After Nondiagnostic Short-Read Genome Sequencing in Infants With Unexplained Epilepsy.Neurology · 2026Article
- Atrophin-1 antisense oligonucleotide provides robust protection from pathology in a fully humanized DRPLA model.Molecular therapy. Nucleic acids · 2026Article
- Repeat-associated non-AUG translation as a common mechanism for the polyGln ataxias.Cell reports · 2026Article
- Treatment of primary adult-onset neurodegenerative cerebellar ataxias.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Predicting disease progression in progressive cerebellar ataxias: integrating clinical, imaging, fluid, genetic, and digital biomarkers.Frontiers in neurology · 2026Review
- Multiomics approach identifies SERPINB1 as candidate biomarker for spinocerebellar ataxia type 2.Scientific reports · 2025Article
- Cell replacement in the degenerating cerebellum: a historical essay of discovery.Journal of neurology · 2025Review
- At-home wearables and machine learning capture motor impairment and progression in adult ataxias.Brain : a journal of neurology · 2025Article
- A human Staufen1 BAC transgenic mouse exhibits abnormal autophagy and neurodegeneration across the central nervous system.Research square · 2025Article
- Fto-mediated mJournal of biomedical science · 2025Article
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123 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
There are no disease-modifying treatments for adult human neurodegenerative diseases. Here we test RNA-targeted therapies in two mouse models of spinocerebellar ataxia type 2 (SCA2), an autosomal dominant polyglutamine disease. Both models recreate the progressive adult-onset dysfunction and degeneration of a neuronal network that are seen in patients, including decreased firing frequency of cerebellar Purkinje cells and a decline in motor function. We developed a potential therapy directed at the ATXN2 gene by screening 152 antisense oligonucleotides (ASOs). The most promising oligonucleotide, ASO7, downregulated ATXN2 mRNA and protein, which resulted in delayed onset of the SCA2 phenotype. After delivery by intracerebroventricular injection to ATXN2-Q127 mice, ASO7 localized to Purkinje cells, reduced cerebellar ATXN2 expression below 75% for more than 10 weeks without microglial activation, and reduced the levels of cerebellar ATXN2. Treatment of symptomatic mice with ASO7 improved motor function compared to saline-treated mice. ASO7 had a similar effect in the BAC-Q72 SCA2 mouse model, and in both mouse models it normalized protein levels of several SCA2-related proteins expressed in Purkinje cells, including Rgs8, Pcp2, Pcp4, Homer3, Cep76 and Fam107b. Notably, the firing frequency of Purkinje cells returned to normal even when treatment was initiated more than 12 weeks after the onset of the motor phenotype in BAC-Q72 mice. These findings support ASOs as a promising approach for treating some human neurodegenerative diseases.
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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.