Myogenic stem cells for the therapy of primary myopathies: wishful thinking or therapeutic perspective?

Primary myopathies are characterized by a progressive wasting of skeletal muscle that leads to deterioration of movements and, in the most severe cases, such as in Duchenne’s muscular dystrophy (DMD), to complete paralysis and death. Most myopathies in which the molecular defect has been identified are due to mutations affecting proteins that form a supramolecular link between the cytoskeleton and the extracellular matrix, such as dystrophin, the mutated protein in DMD. In the absence of one of these proteins, mechanical stress associated with contraction progressively leads to degeneration of the muscle fiber, although the underlying mechanisms are still poorly understood. In the first phase of the disease, new muscle fibers are formed by fusion of resident myoblasts, called satellite cells, which also bear the molecular defect of the fibers that they replace, and hence undergo the same fate. Once the proliferation potential of satellite cells is exhausted, there is no further regeneration and the skeletal muscle is replaced by connective tissue