Improvement of motor conduction velocity in hereditary neuropathy of LAMA2-CMD dy2J/dy2J mouse model by glatiramer acetate

Abstract

ObjectiveGlatiramer acetate (GA), an agent modulating the immune system, has been shown to cause significantly improved mobility and hind limb muscle strength in the dy2J/dy2J mouse model for LAMA2-congenital muscular dystrophy (LAMA2-CMD). In view of these findings and the prominent peripheral nervous system involvement in this laminin-α2 disorder we evaluated GA’s effect on dy2J/dy2J motor nerve conduction electrophysiologically. MethodsLeft sciatic-tibial motor nerve conduction studies were performed on wild type (WT) mice (n = 10), control dy2J/dy2J mice (n = 11), and GA treated dy2J/dy2J mice (n = 10) at 18 weeks of age. ResultsControl dy2J/dy2J mice average velocities (34.49 ± 2.15 m/s) were significantly slower than WT (62.57 ± 2.23 m/s; p < 0.0005), confirming the clinical observation of hindlimb paresis in dy2J/dy2J mice attributed to peripheral neuropathy. GA treated dy2J/dy2J mice showed significantly improved average sciatic-tibial motor nerve conduction velocity versus control dy2J/dy2J (50.35 ± 2.9 m/s; p < 0.0005). ConclusionIn this study we show for the first time improvement in motor nerve conduction velocity of LAMA2-CMD dy2J/dy2J mouse model’s hereditary peripheral neuropathy following GA treatment. SignificanceThis study suggests a possible therapeutic effect of glatiramer acetate on hereditary peripheral neuropathy in this laminin-α2 disorder.