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Immunomodulation by the copolymer glatiramer acetate
Author(s) -
Ar Ruth,
Sela Michael
Publication year - 2003
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.628
Subject(s) - glatiramer acetate , multiple sclerosis , immunology , myelin basic protein , myelin , major histocompatibility complex , medicine , autoimmune encephalitis , immune system , antigen , proteolipid protein 1 , pharmacology , antibody , autoantibody , central nervous system
Glatiramer acetate (GA; Copaxone®, also known as Copolymer 1 or Cop‐1), a copolymer of amino acids, is very effective in the suppression of experimental autoimmune encephalitis (EAE), the animal model for multiple sclerosis (MS), in various species including primates. The immunological cross‐reaction between the myelin basic protein and GA serves as the basis for the suppressive activity of GA in EAE, by the induction of antigen‐specific suppressor cells. The mode of action of GA is by initial strong promiscuous binding to major histocompatibility complex class II molecules and competition with MBP and other myelin proteins for such binding and presentation to T cells. Suppressor T cells induced by GA are of the Th2 type, migrate to the brain and lead to in situ bystander suppression. Clinical trials with GA, both phase II and phase III, were performed in relapsing–remitting MS (RRMS) patients, and demonstrated efficacy in reducing the relapse rate, decreasing MRI‐assessed disease activity and burden and slowing progression of disability. GA is generally well tolerated and is not associated with influenza‐like symptoms and formation of neutralizing antibodies seen with β‐interferons. It exerts its suppressive effect primarily by immunomodulation, and has recently shown ameliorating effect in a few additional autoimmune disorders as well as in graft rejection. At present GA is considered a valuable first‐line treatment option for patients with RRMS. Copyright © 2003 John Wiley & Sons, Ltd.