ABSTRACT
Degeneration and regeneration of skeletal muscle fibers is a distinguishing feature of muscular dystrophies and is particularly conspicuous in Duchenne and Becker muscular dystrophies (DMD and BMD). Moreover, much of the clinical compromise of muscular function arising in these conditions is attributable to a progressive failure of the regenerative aspect of this process. This is manifest in two ways: first, there appears to be a diminution of myogenic potential resident in the muscles, and second, there is not merely a failure to produce sufficient muscle, but the muscle bulk is progressively replaced by fibrous scar and fatty tissue. Whether this second feature is mechanistically linked to the first, i.e., by derangement of the myogenic cell program toward fibrogenic and adipocytic fates, or is an opportunistic takeover of available space by independently determined fibrogenic and adipocytic cells, is a moot point (1,2). Resolution of this question is clearly important in determining the precise approach to be adopted to counteract the loss of muscle. In the former case, one would aim to block the transdifferentiation of myogenic cells, while in the second they would need to be supplemented in some way. Whatever the case, any comprehensive therapy for any but the youngest cases of DMD and BMD must address the issue of rescuing the failing myogenic response, but the precise means by which this
can best be accomplished will depend on the exact nature of the disruption of the natural myogenic mechanisms. In addition, over the past few years, support has been provided for the argument that enhancing myogenesis in dystrophic muscles can be of benefit. This is made explicit in the notion that increasing the strength of muscles to above normal levels will reduce the stress placed on individual muscle fibers by day-to-day activity and thus reduce their susceptibility to necrosis, prolonging their average lifespan and reducing the inflammatory consequences of tissue injury (3,4).
