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

Abstract

Objective: Glatiramer acetate (GA), an agent modulating the immune system, has been shown to cause significantly improved mobility and hind limb muscle strength in the dy^2J/dy^2J 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 dy^2J/dy^2J motor nerve conduction electrophysiologically.

Methods: Left sciatic-tibial motor nerve conduction studies were performed on wild type (WT) mice (n = 10), control dy^2J/dy^2J mice (n = 11), and GA treated dy^2J/dy^2J mice (n = 10) at 18 weeks of age.

Results: Control dy^2J/dy^2J 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 dy^2J/dy^2J mice attributed to peripheral neuropathy. GA treated dy^2J/dy^2J mice showed significantly improved average sciatic-tibial motor nerve conduction velocity versus control dy^2J/dy^2J (50.35 ± 2.9 m/s; p < 0.0005).

Conclusion: In this study we show for the first time improvement in motor nerve conduction velocity of LAMA2-CMD dy^2J/dy^2J mouse model's hereditary peripheral neuropathy following GA treatment.

Significance: This study suggests a possible therapeutic effect of glatiramer acetate on hereditary peripheral neuropathy in this laminin-α2 disorder.

Keywords: Glatiramer acetate; LAMA2-congenital muscular dystrophy; Nerve conduction; Peripheral neuropathy; dy(2J)/dy(2J) mice.