Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD), which occurs in approximately 1 in 3500-5000 live male births, causes a lack of functional dystrophin that leads to stress and tears of muscle cell membranes, resulting in muscle cell death. The dystrophin protein maintains the integrity of muscle fibers and acts as a shock absorber through its role as the foundation of a group of proteins that connects the inner and outer elements of muscle cells. DMD patients suffer from progressive muscle weakness that typically starts in boys at a very young age. Those living with the condition often require special aid and assistance throughout their lives and have significantly shortened life expectancy.

We are developing AOCs to treat the underlying cause of DMD. The oligonucleotides in our AOCs are designed to promote the skipping of specific exons to allow the production of the dystrophin gene product in patients with DMD. In preclinical studies, we observed that treatment of an mdx mouse, a widely used animal model for DMD, with an AOC caused a greater than 50-fold increase in exon skipping compared to an equimolar dose of the unconjugated oligonucleotide.