Purpose of review: As the first genetic disease for which the culpable gene was identified by positional cloning, Duchenne muscular dystrophy has served as a paradigm for therapeutic approaches to neuromuscular disease, in which role it has proved especially testing. The large mass and broad distribution of the target tissue, skeletal muscle, have stretched the patience and ingenuity of those seeking therapeutic delivery of the largest known gene. The most promising recent advances are summarized in this article.
Recent findings: The main obstacle to genetic therapies has been the development of vectors able to efficiently deliver large, potentially therapeutic, genetic constructs to the large and widely dispersed mass of body musculature. Recombinant viral vectors that efficiently transduce muscle are unable to carry the full-length construct. Myogenic cells that are able both to carry full-length genes and to repair muscles are technically challenging to produce in sufficient quantity. A recent promising approach is the use of agents that obviate the mutation.
Summary: Although genetic and cell-mediated approaches are currently showing genuine promise in preclinical and clinical trials, there remains considerable interest in the development of agents that ameliorate the downstream pathology. One general challenge is the three-way tension between the interests of patients, regulators, and the biotechnology industry.