Somatic gene therapy to treat heart failure is one step closer to reality

Despite recent advances in heart failure therapy, patients with end-stage cardiac failure have a poor prognosis and die within 5 years. Diagnosis of the hereditary form of heart failure is becoming increasingly prevalent due to the identification of causative mutations in many structural genes encoding contractile and cytoskeletal proteins. The majority of muscular dystrophies including Duchenne muscular dystrophy (DMD) cause functional deficits not only in skeletal muscle but also in cardiac muscle since the proteins affected are normally present in all striated muscle. DMD is caused by mutations in the very large dystrophin gene. Dystrophin binds the submembranous cytoskeleton at one end and at the other end to a complex of membrane glycoproteins ( Figure 1 ) called the dystrophin-associated glycoprotein complex (DGC). The DGC plays an essential role in maintaining the integrity of the cell membrane by forming a structural link between the extracellular matrix and the cytoskeleton, and in this way, the entire complex transduces the force of contraction and thereby protects the cell membrane from damage. Mutations in dystrophin and several other members of this complex, known as the sarcoglycans, destabilize the entire complex from the membrane and cause both skeletal and cardiac myopathies characterizing DMD and limb-girdle muscular dystrophies. In addition to causing muscular dystrophies, certain mutations in dystrophin and DGC lead primarily to … *Corresponding author. Tel: +1 614 292 2310; fax: +1 614 292 4888. E-mail address : periasamy.1{at}osu.edu