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Citation Information: JCI Insight. 2023;8(21):e165974. https://doi.org/10.1172/jci.insight.165974.
Abstract
New medicines are urgently required to treat the fatal neuromuscular disease Duchenne muscular dystrophy (DMD). Dimethyl fumarate (DMF) is a potent immunomodulatory small molecule nuclear erythroid 2-related factor 2 activator with current clinical utility in the treatment of multiple sclerosis and psoriasis that could be effective for DMD and rapidly translatable. Here, we tested 2 weeks of daily 100 mg/kg DMF versus 5 mg/kg standard-care prednisone (PRED) treatment in juvenile mdx mice with early symptomatic DMD. Both drugs modulated seed genes driving the DMD disease program and improved force production in fast-twitch muscle. However, only DMF showed pro-mitochondrial effects, protected contracting muscles from fatigue, improved histopathology, and augmented clinically compatible muscle function tests. DMF may be a more selective modulator of the DMD disease program than PRED, warranting follow-up longitudinal studies to evaluate disease-modifying impact.
Authors
Cara A. Timpani, Stephanie Kourakis, Danielle A. Debruin, Dean G. Campelj, Nancy Pompeani, Narges Dargahi, Angelo P. Bautista, Ryan M. Bagaric, Elya J. Ritenis, Lauren Sahakian, Didier Debrincat, Nicole Stupka, Patricia Hafner, Peter G. Arthur, Jessica R. Terrill, Vasso Apostolopoulos, Judy B. de Haan, Nuri Guven, Dirk Fischer, Emma Rybalka
Usage data is cumulative from December 2023 through December 2024.
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|---|---|---|
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| Supplemental data | 85 | 14 |
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| Total Views | 2,547 | |
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