ArticleNucleic acids research2020
Potent and sustained huntingtin lowering via AAV5 encoding miRNA preserves striatal volume and cognitive function in a humanized mouse model of Huntington disease.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- SHMT2 deficiency disrupts transcriptional regulation through homocysteine-mediated suppression of histone lactylation in Huntington's disease models.The Journal of clinical investigation · 2026Article
- MicroRNAs and Long Non-Coding RNAs Affect the Mechanisms Involved in Age-Related Neurodegeneration in a Manner Depending on RNA-Binding Proteins.Molecular neurobiology · 2026Review
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.bioRxiv : the preprint server for biology · 2025Article
- Molecular and imaging biomarker responses to brain mutant HTT lowering in a mouse model of Huntington disease.Molecular therapy. Nucleic acids · 2025Article
- MicroRNAs in neurodegenerative diseases: from molecular mechanisms to clinical biomarkers, detection methods and therapeutic strategies-advances and challenges.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Revolutionizing Huntington's Disease Treatment: Breakthroughs in AAV-Mediated Gene Therapy.Cells · 2025Review
- The Role of MicroRNAs in Neurodegeneration: Insights from Huntington's Disease.Molecular neurobiology · 2025Review
- Exploring immunotherapeutic strategies for neurodegenerative diseases: a focus on Huntington's disease and Prion diseases.Acta pharmacologica Sinica · 2025Review
- In Vitro Efficacy of PEI-Derived Lipopolymers in Silencing of Toxic Proteins in a Neuronal Model of Huntington's Disease.Pharmaceutics · 2025Article
- Advances in gene and cellular therapeutic approaches for Huntington's disease.Protein & cell · 2025Review
- Exon 1-targeting miRNA reduces the pathogenic exon 1 HTT protein in Huntington's disease models.Brain : a journal of neurology · 2024Article
- Advances in the roles and mechanisms of mesenchymal stem cell derived microRNAs on periodontal tissue regeneration.Stem cell research & therapy · 2024Review
- Neuroinflammatory Proteins in Huntington's Disease: Insights into Mechanisms, Diagnosis, and Therapeutic Implications.International journal of molecular sciences · 2024Review
- Elevated plasma and CSF neurofilament light chain concentrations are stabilized in response to mutant huntingtin lowering in the brains of Huntington's disease mice.Translational neurodegeneration · 2024Article
- Glucose metabolism in glioma: an emerging sight with ncRNAs.Cancer cell international · 2024Review
- Gene therapy for ultrarare diseases: a geneticist's perspective.Journal of biomedical science · 2024Review
- Neurosurgical gene therapy for central nervous system diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Molecular Mechanisms in the Design of Novel Targeted Therapies for Neurodegenerative Diseases.Current issues in molecular biology · 2024Review
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington disease (HD) is a fatal neurodegenerative disease caused by a pathogenic expansion of a CAG repeat in the huntingtin (HTT) gene. There are no disease-modifying therapies for HD. Artificial microRNAs targeting HTT transcripts for degradation have shown preclinical promise and will soon enter human clinical trials. Here, we examine the tolerability and efficacy of non-selective HTT lowering with an AAV5 encoded miRNA targeting human HTT (AAV5-miHTT) in the humanized Hu128/21 mouse model of HD. We show that intrastriatal administration of AAV5-miHTT results in potent and sustained HTT suppression for at least 7 months post-injection. Importantly, non-selective suppression of huntingtin was generally tolerated, however high dose AAV5-miHTT did induce astrogliosis. We observed an improvement of select behavioural and modest neuropathological HD-like phenotypes in Hu128/21 mice, suggesting a potential therapeutic benefit of miRNA-mediated non-selective HTT lowering. Finally, we also observed that potent reduction of wild type HTT (wtHTT) in Hu21 control mice was tolerated up to 7 months post-injection but may induce impairment of motor coordination and striatal atrophy. Taken together, our data suggests that in the context of HD, the therapeutic benefits of mHTT reduction may outweigh the potentially detrimental effects of wtHTT loss following non-selective HTT lowering.
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