ArticlePloS one2017
The expanded CAG repeat in the huntingtin gene as target for therapeutic RNA modulation throughout the HD mouse brain.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 70 citations in OpenAlex.
- Sex-dependent mild cardiac dysfunction and neurometabolic abnormalities in a model of Huntington's disease.Disease models & mechanisms · 2026Article
- An acyclic nucleic acid-modified siRNA targeting CAG expansions for polyglutamine disease treatment.Molecular therapy. Nucleic acids · 2026Article
- 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
- Accurate Quantification of Mutant and Wild-Type polyQ Proteins Using Simple Western Capillary Immunoassays.Molecular neurobiology · 2025Article
- Exploring immunotherapeutic strategies for neurodegenerative diseases: a focus on Huntington's disease and Prion diseases.Acta pharmacologica Sinica · 2025Review
- Advances in gene and cellular therapeutic approaches for Huntington's disease.Protein & cell · 2025Review
- Evaluation of an Antisense Oligonucleotide Targeting CAG Repeats: A Patient-Customized Therapy Study for Huntington's Disease.Life (Basel, Switzerland) · 2024Article
- Therapeutic targeting of RNA for neurological and neuromuscular disease.Genes & development · 2024Review
- AAV-Mediated CAG-Targeting Selectively Reduces Polyglutamine-Expanded Protein and Attenuates Disease Phenotypes in a Spinocerebellar Ataxia Mouse Model.International journal of molecular sciences · 2024Article
- Latest advances on new promising molecular-based therapeutic approaches for Huntington's disease.Journal of translational internal medicine · 2024Article
- Huntington's Disease Clinical Trials Corner: March 2024.Journal of Huntington's disease · 2024Article
- 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
- Benefits of global mutant huntingtin lowering diminish over time in a Huntington's disease mouse model.JCI insight · 2022Article
- Therapeutic Strategies in Huntington's Disease: From Genetic Defect to Gene Therapy.Biomedicines · 2022Review
- Potential disease-modifying therapies for Huntington's disease: lessons learned and future opportunities.The Lancet. Neurology · 2022Review
- Impact of ER Stress and ER-Mitochondrial Crosstalk in Huntington's Disease.International journal of molecular sciences · 2022Review
- Emerging Therapies for Huntington's Disease - Focus on N-Terminal Huntingtin and Huntingtin Exon 1.Biologics : targets & therapy · 2022Review
- Current and Possible Future Therapeutic Options for Huntington's Disease.Journal of central nervous system disease · 2022Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of these studies was to demonstrate the therapeutic capacity of an antisense oligonucleotide with the sequence (CUG)7 targeting the expanded CAG repeat in huntingtin (HTT) mRNA in vivo in the R6/2 N-terminal fragment and Q175 knock-in Huntington's disease (HD) mouse models. In a first study, R6/2 mice received six weekly intracerebroventricular infusions with a low and high dose of (CUG)7 and were sacrificed 2 weeks later. A 15-60% reduction of both soluble and aggregated mutant HTT protein was observed in striatum, hippocampus and cortex of (CUG)7-treated mice. This correction at the molecular level resulted in an improvement of performance in multiple motor tasks, increased whole brain and cortical volume, reduced levels of the gliosis marker myo-inositol, increased levels of the neuronal integrity marker N-aceyl aspartate and increased mRNA levels of the striatal marker Darpp-32. These neuroanatomical and neurochemical changes, together with the improved motor performance, suggest that treatment with (CUG)7 ameliorates basal ganglia dysfunction. The HTT-lowering was confirmed by an independent study in Q175 mice using a similar (CUG)7 AON dosing regimen, further demonstrating a lasting reduction of mutant HTT protein in striatum, hippocampus and cortex for up to 18 weeks post last infusion along with an increase in motor activity. Based on these encouraging results, (CUG)7 may thus offer an interesting alternative HTT-lowering strategy for HD.
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