Progress in Gene Therapy for Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD), a debilitating and ultimately fatal neuromuscular disorder, is genetically heterogeneous, resulting from deletions, duplications, and point mutations that disrupt the open reading frame of the dystrophin gene. The resulting deficiency of the essential sarcolemmal protein dystrophin leads to muscle inflammation and degeneration. In Becker muscular dystrophy, a milder form of the disease, mutations in the dystrophin gene do not disrupt the open reading frame. These observations led to the use of splice-switching synthetic oligonucleotides known as morpholino oligomers to induce exon skipping, with promising results in both animal models of DMD and in vitro studies. To test the safety of the morpholino oligom…