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醋酸格拉替雷:从实验室到临床再回归

Glatiramer Acetate: from Bench to Bed and Back.

作者信息

Arnon Ruth, Aharoni Rina

机构信息

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

出版信息

Isr Med Assoc J. 2019 Mar;21(3):151-157.

Abstract

Glatiramer acetate (GA, Copaxone®, Copolymer1, Cop 1) is an approved drug for the treatment of relapsing-remitting multiple sclerosis (RRMS). Its efficacy in reducing the frequency of exacerbations and its safety profile establish it as a first-line therapy for MS. Evidence from the animal model experimental autoimmune encephalomyelitis (EAE) and from MS patients indicate that GA affects various levels of the innate and the adaptive immune response, inducing deviation from the pro-inflammatory to the anti-inflammatory pathways. This includes mainly the induction of Th2/3 and T-regulatory cells, and down-regulation of both Th1 and Th17 cells. The immune cells induced by GA reach the CNS and secrete in situ anti-inflammatory cytokines, alleviating the pathological processes. In addition to its immunomodulatory activities, GA promotes neuroprotective repair processes such as secretion of neurotrophic factors, remyelination and neurogenesis, indicating that repair process in the CNS can be up-regulated by therapy.

摘要

醋酸格拉替雷(GA,考帕松®,共聚物1,Cop 1)是一种已获批准用于治疗复发缓解型多发性硬化症(RRMS)的药物。其在降低病情加重频率方面的疗效及其安全性使其成为MS的一线治疗药物。来自动物模型实验性自身免疫性脑脊髓炎(EAE)和MS患者的证据表明,GA影响先天性和适应性免疫反应的各个层面,促使免疫反应从促炎途径转向抗炎途径。这主要包括诱导Th2/3和调节性T细胞,并下调Th1和Th17细胞。GA诱导的免疫细胞进入中枢神经系统并在局部分泌抗炎细胞因子,减轻病理过程。除了其免疫调节活性外,GA还促进神经保护修复过程,如神经营养因子的分泌、髓鞘再生和神经发生,这表明中枢神经系统的修复过程可通过治疗上调。

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