用醋酸格拉替雷改善 LAMA2-CMD 杂合子突变型遗传性运动感觉神经病小鼠模型的运动神经传导速度。

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

机构信息

Institute of Neurology, Schneider Children's Medical Center of Israel, Tel-Aviv University, 14 Kaplan Street, Petach Tikva 49202, Israel; Pediatric Neuromuscular Laboratory, Felsenstein Medical Research Center, Tel-Aviv University, 14 Kaplan Street, Petach Tikva 49202, Israel.

Pediatric Neuromuscular Laboratory, Felsenstein Medical Research Center, Tel-Aviv University, 14 Kaplan Street, Petach Tikva 49202, Israel.

出版信息

Clin Neurophysiol. 2019 Oct;130(10):1988-1994. doi: 10.1016/j.clinph.2019.07.029. Epub 2019 Aug 16.

DOI:10.1016/j.clinph.2019.07.029

PMID:31476705

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/dy 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/dy motor nerve conduction electrophysiologically.

METHODS

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

RESULTS

Control dy/dy 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/dy mice attributed to peripheral neuropathy. GA treated dy/dy mice showed significantly improved average sciatic-tibial motor nerve conduction velocity versus control dy/dy (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/dy 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.

摘要

目的

已证实，免疫调节剂醋酸格拉替雷可显著改善 LAMA2-先天性肌营养不良（LAMA2-CMD）dy/dy 小鼠模型的活动能力和后肢肌肉力量。鉴于这些发现以及这种层粘连蛋白-α2 紊乱明显涉及周围神经系统，我们评估了 GA 对 dy/dy 运动神经传导的电生理影响。

方法

在 18 周龄时，对野生型（WT）小鼠（n=10）、对照 dy/dy 小鼠（n=11）和 GA 治疗 dy/dy 小鼠（n=10）进行左侧坐骨-胫神经运动神经传导研究。

结果

对照 dy/dy 小鼠的平均速度（34.49±2.15m/s）明显慢于 WT（62.57±2.23m/s；p<0.0005），证实了临床观察到的 dy/dy 小鼠后肢瘫痪归因于周围神经病。GA 治疗的 dy/dy 小鼠的坐骨-胫神经运动神经传导速度与对照 dy/dy 相比有显著提高（50.35±2.9m/s；p<0.0005）。