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June 2005

Glatiramer Acetate Therapy: The Plot Thickens

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Copyright 2005 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2005

Arch Neurol. 2005;62(6):858-859. doi:10.1001/archneur.62.6.858

Glatiramer acetate (Copaxone; Teva Pharmaceuticals, North Wales, Pa) is a random polymer of glutamic acid, lysine, alanine, and tyrosine, and is of considerable interest for its ability to reduce the frequency of relapses in relapsing-remitting multiple sclerosis (MS).1 Several mechanisms have been proposed to explain these findings. Lando et al2 suggested that inhibition of clinical disease in an animal model of MS, experimental autoimmune encephalomyelitis, was due to suppressor cells because protection could be adoptively transferred from glatiramer acetate–treated mice. Early studies suggested that glatiramer acetate could inhibit antigen-specific responses through competition for major histocompatibility complex molecules.3 More recent work suggests that glatiramer acetate treatment of MS patients and mice with experimental autoimmune encephalitis has several potential mechanisms, although the favored one seems to be of inducing a shift in the balance of Th1 and Th2 cells.4,5 However, the exact T-cell populations responsible for these shifts were not characterized immunophenotypically in most of these studies. Glatiramer acetate has been shown to act as an altered peptide ligand and antagonize T-cell clones specific for myelin basic protein 82-100 in vitro.6 In addition, recent studies also propose an effect on antigen-presenting cells, suggesting that the mechanism of action is more complex than mere immune deviation.7,8 It is thus unclear whether glatiramer acetate acts by altering the cytokine phenotype of myelin-reactive T cells, deletes these cells, or induces a regulatory T-cell population which mediates its effects through regulatory cytokines or direct suppression/elimination of target immune populations.

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