Laminin alpha1 chain improves laminin alpha2 chain deficient peripheral neuropathy.
Absence of laminin alpha2 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 alpha1 chain in muscles and the peripheral nervous system of laminin alpha2 chain deficient mice reduced muscular dystrophy and largely corrected the peripheral nerve defects. The presence of laminin alpha1 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 alpha1 chain is an excellent substitute for laminin alpha2 chain in multiple tissues and suggest that treatment with laminin alpha1 chain may be beneficial for MDC1A in humans.
Gawlik
Kinga I
KI
Muscle Biology Unit, Division for Cell and Matrix Biology, Department of Experimental Medical Science, University of Lund, Sweden.
Li
Jia-Yi
JY
Petersén
Asa
A
Durbeej
Madeleine
M
D000818:Animals; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D007797:Laminin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy
D007797:Laminin; C102645:laminin alpha 2; C084098:laminin A