ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Nonallele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington's disease mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers.
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Who cites it
203 citing papers in PubMed, 334 citations in OpenAlex.
- In vivo CRISPR base editing for treatment of Huntington's disease.Nature biomedical engineering · 2026Article
- CRISPR-Cas9-based therapies for Huntington's disease and Friedreich's ataxia: mechanisms, advances, and future perspectives.Neurogenetics · 2026Review
- Nucleic acid therapeutics in neurodegenerative disorders: emerging technologies and clinical landscape.Molecular neurodegeneration advances · 2026Review
- Molecular and imaging biomarker responses to brain mutant HTT lowering in a mouse model of Huntington disease.Molecular therapy. Nucleic acids · 2025Article
- Beyond amyloid: nanobody-mediated neuroinflammatory therapy for Alzheimer's disease.Translational neurodegeneration · 2025Review
- Revolutionizing Huntington's Disease Treatment: Breakthroughs in AAV-Mediated Gene Therapy.Cells · 2025Review
- Current trends in gene therapy to treat inherited disorders of the brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Transcriptome Study in Sicilian Patients with Huntington's Disease.Diagnostics (Basel, Switzerland) · 2025Article
- Recent advances in the development and clinical application of miRNAs in infectious diseases.Non-coding RNA research · 2025Review
- Anti-gene oligonucleotide clamps invade dsDNA and downregulateMolecular therapy. Nucleic acids · 2024Article
- Delivering therapeutic RNA into the brain using extracellular vesicles.Molecular therapy. Nucleic acids · 2024Review
- Advancements in surgical treatments for Huntington disease: From pallidotomy to experimental therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside.Journal of translational medicine · 2024Review
- Preclinical evaluation of stereopure antisense oligonucleotides for allele-selective lowering of mutantMolecular therapy. Nucleic acids · 2024Article
- Global huntingtin knockout in adult mice leads to fatal neurodegeneration that spares the pancreas.Life science alliance · 2024Article
- Sequencing-guided design of genetically encoded small RNAs targeting CAG repeats for selective inhibition of mutantMolecular therapy. Nucleic acids · 2024Article
- Focused Ultrasound-Mediated Disruption of the Blood-Brain Barrier for AAV9 Delivery in a Mouse Model of Huntington's Disease.Pharmaceutics · 2024Article
- Neurodegenerative Diseases: New Hopes and Perspectives.Current molecular medicine · 2024Review
- Early whole-body mutant huntingtin lowering averts changes in proteins and lipids important for synapse function and white matter maintenance in the LacQ140 mouse model.Neurobiology of disease · 2023Article
- Early whole-body mutant huntingtin lowering averts changes in proteins and lipids important for synapse function and white matter maintenance in the LacQ140 mouse model.bioRxiv : the preprint server for biology · 2023Article
143 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Huntington's disease (HD) is a fatal neurodegenerative disease caused by mutant huntingtin (htt) protein, and there are currently no effective treatments. Recently, we and others demonstrated that silencing mutant htt via RNA interference (RNAi) provides therapeutic benefit in HD mice. We have since found that silencing wild-type htt in adult mouse striatum is tolerated for at least 4 months. However, given the role of htt in various cellular processes, it remains unknown whether nonallele-specific silencing of both wild-type and mutant htt is a viable therapeutic strategy for HD. Here, we tested whether cosilencing wild-type and mutant htt provides therapeutic benefit and is tolerable in HD mice. After treatment, HD mice showed significant reductions in wild-type and mutant htt, and demonstrated improved motor coordination and survival. We performed transcriptional profiling to evaluate the effects of reducing wild-type htt in adult mouse striatum. We identified gene expression changes that are concordant with previously described roles for htt in various cellular processes. Also, several abnormally expressed transcripts associated with early-stage HD were differentially expressed in our studies, but intriguingly, those involved in neuronal function changed in opposing directions. Together, these encouraging and surprising findings support further testing of nonallele-specific RNAi therapeutics for HD.
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Registered trials
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