ABSTRACT
Destruction of muscle fibres accompanied by a reactive regenerative response is a major defining characteristic that distinguishes the muscular dystrophies from the more general category of myopathies caused by genetic defects that impact on skeletal muscle.1 In the early stages of severe dystrophies, such as Duchenne muscular dystrophy (DMD), this pathology appears to hold a balance, the regenerative response effectively compensating the loss of muscle fibres. Eventually, however, there is a progressive loss of muscle mass and disruption of structure with consequent physiological dysfunction. This is generally attributed to exhaustion of the proliferative and myogenic competence of resident muscle precursor cells.2,3 Hence, the notion of supplementing these resident cells by grafting of more potent myogenic cells. If these grafted cells were genetically normal or genetically corrected, they would achieve the dual objectives of replacing the failing endogenous myogenic capacity and, at the same time, of introducing normal copies of the defective gene into the newly formed muscle.4'6 A particular advantage arises in the case of skeletal muscle from the fact that muscle fibres are syncytia formed by fusion of the individual myoblasts, for this raises the prospect of each functional copy of the introduced gene spreading its product along the length of the syncytium over several nuclear territories and thus of achieving a disproportionate beneficial effect.
