Modulating fast skeletal muscle contraction protects skeletal muscle in animal models of Duchenne muscular dystrophy
- Author(s): Russell et al.
- Year: 2023
- DOI: 10.1172/JCI153837
- PMID: 36995778
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- Research Areas: Molecular Biology and Pharmacology
- Disease Models: DMD
Overview
Duchenne muscular dystrophy (DMD) results from the absence of dystrophin, leading to membrane injury and a breakdown of muscle fibers. This study investigates the role of fast skeletal muscle contraction in DMD using an orally active inhibitor of fast skeletal muscle myosin, EDG-5506. Even modest reductions in contraction (<15%) are found to protect skeletal muscles in dystrophic mice from stress injury, with long-term treatment decreasing muscle fibrosis. Importantly, therapeutic levels of myosin inhibition with EDG-5506 do not negatively impact strength or coordination. This unexpected finding suggests a potential novel treatment strategy for DMD and related myopathies.