Options for Development of Gene-Based Therapy for Muscular Dystrophy

The gene involved in Duchenne and Becker muscular dystrophies (DMD/ BMD) was the first human gene to be successfully identified by the approach of reverse genetics, or positional cloning (1 ), leading to the recognition of this approach as a valid and useful way of identifying genes for which the biochemical product is unknown. Since then, the genes causing the majority of other MDs have also been mapped, sequenced, and their protein products identified (2 ). Meanwhile, the development of the necessary tools for incorporating genetic material into living cells (gene transfer) has moved from the first attempts to express synthetic reporter genes in cultured cells, through in vivo studies in animal models, to the onset of clinical trials. Indeed, DMD was one of the first inherited diseases thought likely to benefit from gene therapy (GT) (3 ). Although it is now accepted that DMD may be more difficult to treat in this way than some other single-gene disorders, this and other MDs remain suitable candidates for GT for a number of reasons.