Mechanism of action of glatiramer acetate in treatment of multiple sclerosis.
Glatiramer acetate (GA) (Copolymer-1, Copaxone, Teva, Israel, YEAK) is a polypeptide-based therapy approved for the treatment of relapsing-remitting multiple sclerosis. Most investigations have attributed the immunomodulatory effect of GAs to its capability to alter T-cell differentiation. Specifically, GA treatment is believed to promote development of Th2-polarized GA-reactive CD4(+) T-cells, which may dampen neighboring inflammation within the central nervous system. Recent reports indicate that the deficiency in CD4(+)CD25(+)FoxP3(+) regulatory T-cells in multiple sclerosis is restored by GA treatment. GA also exerts immunomodulatory activity on antigen presenting cells, which participate in innate immune responses. These new findings represent a plausible explanation for GA-mediated T-cell immune modulation and may provide useful insight for the development of new and more effective treatment options for multiple sclerosis.
Weber
Martin S
MS
Department of Neurology and Program in Immunology, University of California, San Francisco, CA 94143, USA.
Hohlfeld
Reinhard
R
Zamvil
Scott S
SS
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018448:Models, Immunological; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000503:physiopathology; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate