Immunomodulation by the copolymer glatiramer acetate

Abstract

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 beta-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.