ETEPLIRSEN Inhibitor of Dystrophin Expression Treatment of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an infant-onset X-linked myopathy. Mutations in the dystrophin (DMD) gene disrupt the open reading frame. This leads to a lack of functional protein causing muscle atrophy, ambulatory disturbances and death during the third decade, usually due to associated cardiac and respiratory failure. There are currently no curative solutions for DMD and symptoms are largely managed through steroid use and physical therapy. The development of RNAi technologies including the generation of antisense oligonucleotides has generated a novel class of therapeutics for targeting genetic disorders across a myriad of diseases. These function to overcome genetic mutations, restoring the ability of a mutated gene to produce at least some form of functional protein. Eteplirsen has been developed as a novel antisense phosphorodiamidate morpholino oligomer that induces exon 51 skipping of the dystrophin mRNA transcript to restore the open reading frame and produce a protein that retains partial function. Eteplirsen has shown promising efficacy in preclinical in vivo DMD models and has advanced to clinical evaluation in DMD patients. Clinical phase I/II data indicate its ability to restore some degree of functional dystrophin protein that is associated with improved ambulation and increased quality of life, with no reported adverse events.