ArticleHuman molecular genetics2020
Systemic therapy in an RNA toxicity mouse model with an antisense oligonucleotide therapy targeting a non-CUG sequence within the DMPK 3'UTR RNA.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Elimination of myotonia improves myopathy in a muscleblind-like knockout model of myotonic dystrophy.Nature communications · 2026Article
- Cardiac Involvement in Myotonic Dystrophy Type 1: Mechanisms, Clinical Perspectives, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Elimination of myotonia improves myopathy in a muscleblind knockout model of myotonic dystrophy.bioRxiv : the preprint server for biology · 2025Article
- Promoter-targeted small RNA duplexes increase MBNL1 transcription and mitigate myotonic dystrophy-associated spliceopathy.Nucleic acids research · 2025Article
- Myotonic dystrophies: an update on clinical features, molecular mechanisms, management, and gene therapy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Functions of the Muscleblind-like protein family and their role in disease.Cell communication and signaling : CCS · 2025Review
- Therapeutic advances in type 1 myotonic dystrophy complicated with type 2 diabetes mellitus.Frontiers in neurology · 2025Review
- Studying the Effect of MBNL1 and MBNL2 Loss in Skeletal Muscle Regeneration.International journal of molecular sciences · 2024Article
- Application of Antisense Conjugates for the Treatment of Myotonic Dystrophy Type 1.International journal of molecular sciences · 2023Review
- Establishment of quantitative and consistent in vitro skeletal muscle pathological models of myotonic dystrophy type 1 using patient-derived iPSCs.Scientific reports · 2023Article
- Promising AAV.U7snRNAs vectors targetingFrontiers in cell and developmental biology · 2023Article
- Peptide-Conjugated PMOs for the Treatment of Myotonic Dystrophy.Methods in molecular biology (Clifton, N.J.) · 2023Article
- RNA Transcript Diversity in Neuromuscular Research.Journal of neuromuscular diseases · 2023Review
- Recent Progress and Challenges in the Development of Antisense Therapies for Myotonic Dystrophy Type 1.International journal of molecular sciences · 2022Review
- Myotonic Dystrophy: From Molecular Pathogenesis to Therapeutics.International journal of molecular sciences · 2022Article
- Mice lacking MBNL1 and MBNL2 exhibit sudden cardiac death and molecular signatures recapitulating myotonic dystrophy.Human molecular genetics · 2022Article
- Development of Therapeutic Approaches for Myotonic Dystrophies Type 1 and Type 2.International journal of molecular sciences · 2022Review
- Molecular Therapies for Myotonic Dystrophy Type 1: From Small Drugs to Gene Editing.International journal of molecular sciences · 2022Review
- Cardiac Pathology in Myotonic Dystrophy Type 1.International journal of molecular sciences · 2021Review
- Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Myotonic dystrophy type 1 (DM1), the most common adult muscular dystrophy, is an autosomal dominant disorder caused by an expansion of a (CTG)n tract within the 3' untranslated region (3'UTR) of the dystrophia myotonica protein kinase (DMPK) gene. Mutant DMPK mRNAs are toxic, present in nuclear RNA foci and correlated with a plethora of RNA splicing defects. Cardinal features of DM1 are myotonia and cardiac conduction abnormalities. Using transgenic mice, we have demonstrated that expression of the mutant DMPK 3'UTR is sufficient to elicit these features of DM1. Here, using these mice, we present a study of systemic treatment with an antisense oligonucleotide (ASO) (ISIS 486178) targeted to a non-CUG sequence within the 3'UTR of DMPK. RNA foci and DMPK 3'UTR mRNA levels were reduced in both the heart and skeletal muscles. This correlated with improvements in several splicing defects in skeletal and cardiac muscles. The treatment reduced myotonia and this correlated with increased Clcn1 expression. Furthermore, functional testing showed improvements in treadmill running. Of note, we demonstrate that the ASO treatment reversed the cardiac conduction abnormalities, and this correlated with restoration of Gja5 (connexin 40) expression in the heart. This is the first time that an ASO targeting a non-CUG sequence within the DMPK 3'UTR has demonstrated benefit on the key DM1 phenotypes of myotonia and cardiac conduction defects. Our data also shows for the first time that ASOs may be a viable option for treating cardiac pathology in DM1.
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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.