ArticleThe Journal of clinical investigation2016
Targeting CAG repeat RNAs reduces Huntington's disease phenotype independently of huntingtin levels.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- White matter microstructural alterations in Huntington's disease: a systematic review of diffusion imaging findings.Brain imaging and behavior · 2026Pooled it
- An acyclic nucleic acid-modified siRNA targeting CAG expansions for polyglutamine disease treatment.Molecular therapy. Nucleic acids · 2026Article
- The role of low-complexity repeats in RNA-RNA interactions and a deep learning framework for duplex prediction.Nature communications · 2026Article
- Insights into RNA-mediated pathology in new mouse models of Huntington's disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
- mEMBO reports · 2024Article
- Exploring the Potential Therapeutic Approach Using Ginsenosides for the Management of Neurodegenerative Disorders.Molecular biotechnology · 2024Review
- Latest advances on new promising molecular-based therapeutic approaches for Huntington's disease.Journal of translational internal medicine · 2024Article
- A cyclic pyrrole-imidazole polyamide reduces pathogenic RNA in CAG/CTG triplet repeat neurological disease models.The Journal of clinical investigation · 2023Article
- The length of uninterrupted CAG repeats in stem regions of repeat disease associated hairpins determines the amount of short CAG oligonucleotides that are toxic to cells through RNA interference.Cell death & disease · 2022Article
- A peptide inhibitor that rescues polyglutamine-induced synaptic defects and cell death through suppressing RNA and protein toxicities.Molecular therapy. Nucleic acids · 2022Article
- Asymmetric inheritance of RNA toxicity iniScience · 2022Article
- Mutant huntingtin messenger RNA forms neuronal nuclear clusters in rodent and human brains.Brain communications · 2022Article
- RTP801/REDD1 Is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington's Disease.Biomolecules · 2021Article
- Oligonucleotides Targeting DNA Repeats DownregulateNucleic acid therapeutics · 2021Article
- Gene targeting techniques for Huntington's disease.Ageing research reviews · 2021Review
- Molecular mechanisms underlying nucleotide repeat expansion disorders.Nature reviews. Molecular cell biology · 2021Review
- DNAzyme Cleavage of CAG Repeat RNA in Polyglutamine Diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Selective suppression of polyglutamine-expanded protein by lipid nanoparticle-delivered siRNA targeting CAG expansions in the mouse CNS.Molecular therapy. Nucleic acids · 2021Article
- Huntington's disease brain-derived small RNAs recapitulate associated neuropathology in mice.Acta neuropathologica · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington's disease (HD) is a polyglutamine disorder caused by a CAG expansion in the Huntingtin (HTT) gene exon 1. This expansion encodes a mutant protein whose abnormal function is traditionally associated with HD pathogenesis; however, recent evidence has also linked HD pathogenesis to RNA stable hairpins formed by the mutant HTT expansion. Here, we have shown that a locked nucleic acid-modified antisense oligonucleotide complementary to the CAG repeat (LNA-CTG) preferentially binds to mutant HTT without affecting HTT mRNA or protein levels. LNA-CTGs produced rapid and sustained improvement of motor deficits in an R6/2 mouse HD model that was paralleled by persistent binding of LNA-CTG to the expanded HTT exon 1 transgene. Motor improvement was accompanied by a pronounced recovery in the levels of several striatal neuronal markers severely impaired in R6/2 mice. Furthermore, in R6/2 mice, LNA-CTG blocked several pathogenic mechanisms caused by expanded CAG RNA, including small RNA toxicity and decreased Rn45s expression levels. These results suggest that LNA-CTGs promote neuroprotection by blocking the detrimental activity of CAG repeats within HTT mRNA. The present data emphasize the relevance of expanded CAG RNA to HD pathogenesis, indicate that inhibition of HTT expression is not required to reverse motor deficits, and further suggest a therapeutic potential for LNA-CTG in polyglutamine disorders.
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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.