THE MOLECULAR-BASIS OF ACTIVITY-INDUCED MUSCLE INJURY IN DUCHENNE MUSCULAR-DYSTROPHY

Duchenne muscular dystrophy (DMD) is the most common of the human musc ular dystrophies, affecting approximately 1 in 3500 boys. Most DMD pat ients die in their late teens or early twenties due to involvement of the diaphragm and other respiratory muscles by the disease. The primar y abnormality in DMD is an absence of dystrophin, a 427 kd protein nor mally found at the cytoplasmic face of the muscle cell surface membran e. Based upon the predicted structure and location of the protein, it has been proposed that dystrophin plays an important role in providing mechanical reinforcement to the sarcolemmal membrane of muscle fibers . Therefore, dystrophin could help to protect muscle fibers from poten tially damaging tissue stresses developed during muscle contraction. I n the present paper, the nature of mechanical stresses placed upon myo fibers during various forms of muscle contraction are reviewed, along with current lines of evidence supporting a critical role for dystroph in as a subsarcolemmal membrane-stabilizing protein in this setting. I n addition, the implications of these findings for exercise programs a nd other potential forms of therapy in DMD are discussed.