Molecular, cellular, and pharmacological therapies for Duchenne/Becker muscular dystrophies

Abstract

Although the molecular defect causing Duchenne/Becker muscular dystrophy (DMD/BMD) was identified nearly 20 years ago, the development of effective therapeutic strategies has nonetheless remained a daunting challenge. Over the years, a variety of different approaches have been explored in an effort to compensate for the lack of the DMD gene product called dystrophin. This review not only presents some of the most promising molecular, cellular, and pharmacological strategies but also highlights some issues that need to be addressed before considering their implementation. Specifically, we describe current strategies being developed to exogenously deliver healthy copies of the dystrophin gene to dystrophic muscles. We present the findings of several studies that have focused on repairing the mutant dystrophin gene using various approaches. We include a discussion of cell-based therapies that capitalize on the use of myoblast or stem cell transfer. Finally, we summarize the results of several studies that may eventually lead to the development of appropriate drug-based therapies. In this context, we review our current knowledge of the mechanisms regulating expression of utrophin, the autosomal homologue of dystrophin. Given the complexity associated with the dystrophic phenotype, it appears likely that a combinatorial approach involving different therapeutic strategies will be necessary for the appropriate management and eventual treatment of this devastating neuromuscular disease.