Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene. It is the most common, severe childhood form of muscular dystrophy. Here, the authors investigated an alternative to dystrophin replacement by overexpressing the human α7 integrin gene (ITGA7) using adeno-associated virus (AAV) delivery. ITGA7 is a laminin receptor in skeletal muscle that, like the dystrophin-glycoprotein complex, links the extracellular matrix (ECM) to the internal actin cytoskeleton. ITGA7 is expressed in DMD patients and overexpression does not elicit an immune response to the transgene. They delivered rAAVrh.74.MCK.ITGA7 systemically at 5-7 days of age to the mdx/utrn-/- mouse deficient for dystrophin and utrophin, a severe mouse model of DMD. At eight weeks post injection, widespread expression of ITGA7 was observed at the sarcolemma of multiple muscle groups following gene transfer. The increased expression of ITGA7 significantly extended longevity and reduced common features of the mdx/utrn-/- mouse including kyphosis. Overexpression of α7 expression protected against loss of force following contraction-induced damage and increased specific force in the diaphragm and EDL muscles eight weeks post gene transfer. Taken together, these results further support the use of α7 integrin as a potential therapy for DMD.
