Molecular mechanisms of Duchenne muscular dystrophy and new therapeutic strategies

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease affecting approximately 1 in 5,000 born boys. It is caused by mutations in the DMD gene encoding dystrophin, which protects muscle fibers upon contraction. Its absence leads to muscle weakening and premature death mostly due to cardio-respiratory failure. Many experimental therapies have been developed to restore functional dystrophin or counteract processes contributing to disease progression. Nonetheless, DMD remains an incurable disease, and glucocorticoids, exerting many side effects, still serve as the “gold standard” of treatment. Hence, there is a need to develop innovative therapeutic options that will at least alleviate the symptoms of DMD. Among them, targeting specific microRNAs (miRs), e.g. miR-378a, restoring normal angiogenesis and the use of cytoprotective factors such as heme oxygenase-1 (HO-1) or hydrogen sulfide (H2S) might be of special interest. In this review, we describe both the pathology of the disease and the aforementioned new therapeutic options in DMD.