ArticleHuman molecular genetics2015
Second-generation compound for the modulation of utrophin in the therapy of DMD.
Article in Human molecular genetics, 2015. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Muscle and cardiac therapeutic strategies for Duchenne muscular dystrophy: past, present, and future.Pharmacological reports : PR · 2020Pooled it
- Antisense oligonucleotide selection scheme for rare Duchenne muscular dystrophy mutations: Application toMolecular therapy. Nucleic acids · 2026Article
- Duchenne muscular dystrophy: from gene to gene-ius therapies.Skeletal muscle · 2026Review
- CRISPR-Cas9-mediated upregulation of utrophin ameliorates Duchenne muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Review
- Exploring Desmin as a Potential Modifier in Duchenne Muscular Dystrophy-Associated Cardiomyopathy.Acta physiologica (Oxford, England) · 2025Article
- AAV microdystrophin gene replacement therapy for Duchenne muscular dystrophy: progress and prospects.Gene therapy · 2025Review
- Molecular and Biochemical Therapeutic Strategies for Duchenne Muscular Dystrophy.Neurology international · 2024Review
- Review
- Dystrophin- and Utrophin-Based Therapeutic Approaches for Treatment of Duchenne Muscular Dystrophy: A Comparative Review.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Characterization of disease-specific alterations in metabolites and effects of mesenchymal stromal cells on dystrophic muscles.Frontiers in cell and developmental biology · 2024Article
- Therapeutic approaches for Duchenne muscular dystrophy.Nature reviews. Drug discovery · 2023Review
- Endogenous bioluminescent reporters reveal a sustained increase in utrophin gene expression upon EZH2 and ERK1/2 inhibition.Communications biology · 2023Article
- Identifying FDA-Approved Drugs that Upregulate Utrophin A as a Therapeutic Strategy for Duchenne Muscular Dystrophy.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Inactivation of Sirt6 ameliorates muscular dystrophy in mdx mice by releasing suppression of utrophin expression.Nature communications · 2022Article
- A state-of-the-art review of tamoxifen as a potential therapeutic for duchenne muscular dystrophy.Frontiers in pharmacology · 2022Review
- Utrophin modulator drugs as potential therapies for Duchenne and Becker muscular dystrophies.Neuropathology and applied neurobiology · 2021Article
- Plasma lipidomic analysis shows a disease progression signature in mdx mice.Scientific reports · 2021Article
- Muscular dystrophy: Experimental animal models and therapeutic approaches (Review).Experimental and therapeutic medicine · 2021Review
- Loss of sarcospan exacerbates pathology in mdx mice, but does not affect utrophin amelioration of disease.Human molecular genetics · 2021Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Duchenne muscular dystrophy (DMD) is a lethal, X-linked muscle-wasting disease caused by lack of the cytoskeletal protein dystrophin. There is currently no cure for DMD although various promising approaches are progressing through human clinical trials. By pharmacologically modulating the expression of the dystrophin-related protein utrophin, we have previously demonstrated in dystrophin-deficient mdx studies, daily SMT C1100 treatment significantly reduced muscle degeneration leading to improved muscle function. This manuscript describes the significant disease modifying benefits associated with daily dosing of SMT022357, a second-generation compound in this drug series with improved physicochemical properties and a more robust metabolism profile. These studies in the mdx mouse demonstrate that oral administration of SMT022357 leads to increased utrophin expression in skeletal, respiratory and cardiac muscles. Significantly, utrophin expression is localized along the length of the muscle fibre, not just at the synapse, and is fibre-type independent, suggesting that drug treatment is modulating utrophin transcription in extra-synaptic myonuclei. This results in improved sarcolemmal stability and prevents dystrophic pathology through a significant reduction of regeneration, necrosis and fibrosis. All these improvements combine to protect the mdx muscle from contraction induced damage and enhance physiological function. This detailed evaluation of the SMT C1100 drug series strongly endorses the therapeutic potential of utrophin modulation as a disease modifying therapeutic strategy for all DMD patients irrespective of their dystrophin mutation.
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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 Socratic graph.