ArticlePloS one2014
RNA interference mitigates motor and neuropathological deficits in a cerebellar mouse model of Machado-Joseph disease.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Gene Suppression Therapies in Hereditary Cerebellar Ataxias: A Systematic Review of Animal Studies.Cells · 2023Pooled it
- Extracellular vesicles-associated AAVs for the treatment of Machado-Joseph disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Advances in the Differentiation of hiPSCs into Cerebellar Neuronal Cells.Stem cell reviews and reports · 2024Review
- Extracellular vesicle-based delivery of silencing sequences for the treatment of Machado-Joseph disease/spinocerebellar ataxia type 3.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- A standardised protocol for blood and cerebrospinal fluid collection and processing for biomarker research in ataxia.Neuropathology and applied neurobiology · 2023Article
- Mutant Ataxin-2 Expression in Aged Animals Aggravates Neuropathological Features Associated with Spinocerebellar Ataxia Type 2.International journal of molecular sciences · 2022Article
- miRNA-Mediated Knockdown of ATXN3 Alleviates Molecular Disease Hallmarks in a Mouse Model for Spinocerebellar Ataxia Type 3.Nucleic acid therapeutics · 2022Article
- ULK overexpression mitigates motor deficits and neuropathology in mouse models of Machado-Joseph disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Plasma PolyQ-ATXN3 Levels Associate With Cerebellar Degeneration and Behavioral Abnormalities in a New AAV-Based SCA3 Mouse Model.Frontiers in cell and developmental biology · 2022Article
- Gene therapy for ALS: A review.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Autophagy in Spinocerebellar ataxia type 2, a dysregulated pathway, and a target for therapy.Cell death & disease · 2021Article
- Current Status of Gene Therapy Research in Polyglutamine Spinocerebellar Ataxias.International journal of molecular sciences · 2021Review
- Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3.Science translational medicine · 2020Article
- Genetics, Mechanisms, and Therapeutic Progress in Polyglutamine Spinocerebellar Ataxias.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Spinocerebellar ataxias: prospects and challenges for therapy development.Nature reviews. Neurology · 2018Review
- Allele-specific silencing therapy for Dynamin 2-related dominant centronuclear myopathy.EMBO molecular medicine · 2018Article
- Protein Misfolding and Aggregation as a Therapeutic Target for Polyglutamine Diseases.Brain sciences · 2017Review
- Polyglutamine spinocerebellar ataxias - from genes to potential treatments.Nature reviews. Neuroscience · 2017Review
- Unravelling Endogenous MicroRNA System Dysfunction as a New Pathophysiological Mechanism in Machado-Joseph Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Primary and secondary ataxias.Current opinion in neurology · 2015Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Machado-Joseph disease or Spinocerebellar ataxia type 3 is a progressive fatal neurodegenerative disorder caused by the polyglutamine-expanded protein ataxin-3. Recent studies demonstrate that RNA interference is a promising approach for the treatment of Machado-Joseph disease. However, whether gene silencing at an early time-point is able to prevent the appearance of motor behavior deficits typical of the disease when initiated before onset of the disease had not been explored. Here, using a lentiviral-mediated allele-specific silencing of mutant ataxin-3 in an early pre-symptomatic cerebellar mouse model of Machado-Joseph disease we show that this strategy hampers the development of the motor and neuropathological phenotypic characteristics of the disease. At the histological level, the RNA-specific silencing of mutant ataxin-3 decreased formation of mutant ataxin-3 aggregates, preserved Purkinje cell morphology and expression of neuronal markers while reducing cell death. Importantly, gene silencing prevented the development of impairments in balance, motor coordination, gait and hyperactivity observed in control mice. These data support the therapeutic potential of RNA interference for Machado-Joseph disease and constitute a proof of principle of the beneficial effects of early allele-specific silencing for therapy of this disease.
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