Merosin-deficient congenital muscular dystrophy type-1A (MDC1A) is characterised by progressive muscular dystrophy and dysmyelinating neuropathy caused by mutations of the α2 chain of laminin-211, the predominant laminin isoform of muscles and nerves. MDC1A has no available treatment so far, although preclinical studies showed amelioration of the disease by the overexpression of miniagrin (MAG). MAG reconnects orphan laminin-211 receptors to other laminin isoforms available in the extracellular matrix of MDC1A mice. In this study, mesoangioblasts (MABs) were engineered to overexpress MAG to treat MDC1A mouse models, thus combining cell to gene therapy. Treated mice showed diffuse expression of mMAG at the sarcolemma surface and increased expression of laminin-211 receptors. Significant amelioration of muscle histology and reduced deterioration of motor performances were observed, whereas no effects on peripheral neuropathy were noted. This proof of principle study demonstrates the potential efficacy of combining cell with gene therapy to treat MDC1A.
