Mechanisms of action of glatiramer acetate in multiple sclerosis

被引:211
作者
Neuhaus, O
Farina, C
Wekerle, H
Hohlfeld, R
机构
[1] Max Planck Inst Neurobiol, Dept Neuroimmunol, Martinsried, Germany
[2] Univ Munich, Inst Clin Neuroimmunol, Munich, Germany
[3] Univ Munich, Dept Neurol, Munich, Germany
关键词
D O I
10.1212/WNL.56.6.702
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Glatiramer acetate (GA, Copaxone [Teva Pharmaceuticals, Kansas City, MO], formerly known as copolymer-1) and interferon- (IFN)-beta are both used for the immunomodulatory treatment of multiple sclerosis, but they act in different ways. Four major mechanisms of GA have been identified: 1) competition with myelin-basic protein (MBP) for binding to major histocompatibility complex (MHC) molecules; 2) competition of GA/MHC with MBP/MHC for binding to the T-cell receptor; 3) partial activation and tolerance induction of MBP-specific T cells (action as an altered peptide ligand); and 4) induction of GA-reactive T-helper 2- (TH2)-like regulatory cells. Of these four mechanisms, 1 and 2 presumably occur only in vitro and are therefore irrelevant for the in vivo effects of GA. In contrast, mechanisms 3 and 4 could occur in vivo and both could contribute to the clinical effects of GA.
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页码:702 / 708
页数:7
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