Dimethyl fumarate modulates the dystrophic disease program following short-term treatment.

2023-11-08

Timpani, Cara A

Kourakis, Stephanie

Debruin, Danielle A

Campelj, Dean G

Pompeani, Nancy

Dargahi, Narges

Bautista, Angelo Patrick R

Bagaric, Ryan M

Ritenis, Elya J

Sahakian, Lauren

Debrincat, Didier

Stupka, Nicole

Hafner, Patricia

Arthur, Peter G

Terrill, Jessica R

Apostolopoulos, Vasso

De Haan, Judy B

Gueven, Nuri

Fischer, Dirk

Rybalka, Emma

Drug therapy

Muscle Biology

Neuromuscular disease

Skeletal muscle

Therapeutics

Journal Article

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10.1172/jci.insight.165974

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 (Nrf2) 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 two weeks of daily 100mg/kg DMF versus 5mg/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.

link

JCI Insight 2023-11-08; 8(21)

JCI Insight

2379-3708