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 Volume 56, Number 6, March 27, 2001
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Neurology 2001;56:702-708
© 2001 American Academy of Neurology
Views & Reviews

Mechanisms of action of glatiramer acetate in multiple sclerosis

Oliver Neuhaus, MD;, Cinthia Farina, PhD;, Hartmut Wekerle, MD; and Reinhard Hohlfeld, MD

From the Department of Neuroimmunology (Drs. Neuhaus, Farina, Wekerle, and Hohlfeld), Max-Planck Institute of Neurobiology, Martinsried; and the Institute for Clinical Neuroimmunology and the Department of Neurology (Dr. Hohlfeld), Ludwig Maximilians University, Munich, Germany.

Address correspondence and reprint requests to Dr. Reinhard Hohlfeld, Institute for Clinical Neuroimmunology, Klinikum Grosshadern, Ludwig Maximilians University, Marchioninistrasse 15, 81366 Munich, Germany; e-mail: hohlfeld{at}neuro.mpg.de

Glatiramer acetate (GA, Copaxone [Teva Pharmaceuticals, Kansas City, MO], formerly known as copolymer-1) and interferon- (IFN)-ß 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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