Laminin α1 chain improves laminin α2 chain deficient peripheral neuropathy

Absence of laminin alpha 2 chain leads to a severe form of congenital muscular dystrophy (MDC1A) associated with peripheral neuropathy. Hence, future therapies should be aimed at alleviating both muscle and neurological dysfunctions. Pre-clinical studies in animal models have mainly focused on ameliorating the muscle phenotype. Here we show that transgenic expression of laminin alpha 1 chain in muscles and the peripheral nervous system of laminin alpha 2 chain deficient mice reduced muscular dystrophy and largely corrected the peripheral nerve defects. The presence of laminin alpha 1 chain in the peripheral nervous system resulted in near-normal myelination, restored Schwann cell basement membranes and improved rotarod performance. In summary, we postulate that laminin alpha 1 chain is an excellent substitute for laminin alpha 2 chain in multiple tissues and suggest that treatment with laminin alpha 1 chain may be beneficial for MDC1A in humans.