Adenovirus Vectors for Therapeutic Gene Transfer to Skeletal Muscles
Josephine Nalbantoglu, Basil J. Petrof, Rénald Gilbert, and George Karpati
Duchenne’s muscular dystrophy (DMD) and the less severe Becker muscular dystrophy (BMD) result from mutations in the dystrophin gene on chromosome Xp21.1 DMD, which afflicts approximately 1 in 3,500 male newborns, is fatal by the third decade of life in most patients, usually due to severe weakness of the diaphragm and other respiratory muscles. The subsarcolemmal protein dystrophin plays an important role in structural reinforcement of the muscle cell surface membrane by providing a structural linkage between cytoplasmic actin and the extracellular matrix, via binding of the dystrophin-associated protein complex (DPC) which spans the membrane of muscle fibers. Although precise function of dystrophin in muscle remains somewhat controversial, it is generally believed that skeletal muscles lacking dystrophin are abnormally susceptible to contraction-induced damage of the sarcolemma, which secondarily leads to muscle fiber dysfunction, necrosis and eventual replacement of the lost fibers by connective tissue.