The researchers from the University of Pittsburgh used a state-of-theart adeno-associated viral (AAV) vector to systemically deliver mini-agrin, whose efficacy for the treatment had been demonstrated earlier in transgenic mice. 2, 3 Their work impressively demonstrates the feasibility of systemic gene delivery for long-term transduction of skeletal and cardiac muscle and subsequent substantial amelioration of the disease without any additional pharmacological intervention. This work points the way to a new approach to gene therapy for patients suffering from MDC1A.

MDC1A is an autosomal recessive muscle wasting disease that often leads to death in early childhood. It is caused by mutations in LAMA2, the gene encoding laminin a2, which assembles with the b1 and the g1 chain to laminin-2, the main laminin isoform present in the basement membrane of muscle fibers and peripheral nerves (Figure 1a). Basement membranes are highly structured sheets of extracellular matrix molecules that surround many cells. Although other laminin isoforms are synthesized in the muscle of MDC1A patients, they do not form a proper basement membrane that is connected to the muscle sarcolemmal membrane (Figure 1b). Hence, the chain of proteins linking the actin cytoskeleton via the sarcolemma to the basement membrane is inter-