Moderate-term dimethyl fumarate treatment reduces pathology of dystrophic skeletal and cardiac muscle in a mouse model

Abstract

There has been a wave of new therapeutics in Duchenne muscular dystrophy (DMD) that target the genetic, (missing) protein and flow-on pathogenic mechanisms emerging recently. These medicines will be vital to extend lifespan complementary to corticosteroids, which have been used as a standard of care tool for more than 30 years. While corticosteroids significantly slow disease progression, they also impart side effects severe enough to preclude use in some patients. We have previously demonstrated that short-term treatment with dimethyl fumarate (DMF), a drug with indication and established safety data in Multiple Sclerosis, more selectively modulates Duchenne (mdx) immunology than the frequently used corticosteroid, prednisone. Here, we assess the effect of moderate-term DMF treatment over 5 weeks in exercise-aggravated mdx mice. We show that like prednisone, DMF maintains anti-inflammatory, anti-fibrotic, and anti-lipogenic activity on muscle with moderate-term use but does not reduce muscle degeneration per se. This study supports our previous work highlighting DMF as a possible repurposing candidate for DMD, especially for patients who cannot tolerate chronic corticosteroid treatment.