@article{49a97a235a324a91948ce2db52e1f3a9,
title = "Dimethyl fumarate modulates the dystrophic disease program following short-term treatment",
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.",
author = "Timpani, {Cara A.} and Stephanie Kourakis and Debruin, {Danielle A.} and Campelj, {Dean G.} and Nancy Pompeani and Narges Dargahi and Bautista, {Angelo P.} and Bagaric, {Ryan M.} and Ritenis, {Elya J.} and Lauren Sahakian and Didier Debrincat and Nicole Stupka and Patricia Hafner and Arthur, {Peter G.} and Terrill, {Jessica R.} and Vasso Apostolopoulos and {de Haan}, {Judy B.} and Nuri Guven and Dirk Fischer and Emma Rybalka",
note = "Funding Information: This work was supported by funding from Victoria University, University Children{\textquoteright}s Hospital Basel, Muscular Dystrophy Association U.S.A. (Ideas grant: MDA871929), Duchenne UK, and Save Our Sons. ER and CAT acknowledge outstanding support from Nicole Christie, Tricia Murphy, and Steven Holloway with animal care and breeding (Victoria University Animal Services, WCHRE, Sunshine Hospital). ER and CAT thank Craig Goodman for donation of the DJ-1 and DJ-1 Cys106 antibodies. All figures were created with BioRender.com. Publisher Copyright: {\textcopyright} 2023, Timpani et al.",
year = "2023",
month = nov,
doi = "10.1172/jci.insight.165974",
language = "English",
volume = "8",
journal = "JCI Insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "21",
}