Glatiramer acetate (Copaxone®) therapy for multiple sclerosis

Glatiramer acetate (GA) (Copaxone(R)) is a worldwide-approved drug for the treatment of relapsing multiple sclerosis (MS), an autoimmune disease of the CNS. The drug is a synthetic copolymer with an amino acid composition based on the structure of myelin basic protein, one of the autoantigens implicated in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE). Developed initially as a "tool" to study EAE, the drug unexpectedly inhibited disease and was subsequently developed for the treatment of MS. The drug has been shown in controlled clinical trials to significantly reduce relapse rate and progression of disability in MS with long-term efficacy, remarkable safety, and tolerability. Efficacy as measured by magnetic resonance imaging parallels its clinical benefits as manifested by a reduction in gadolinium-enhancing lesions and brain atrophy. The mechanism of action of the drug in humans is believed to involve the induction of glatiramer-reactive regulatory cells, including CD4+ and CD8+ T-cells. Glatiramer-reactive Th2 cells are believed to enter the brain and, through cross-reactivity with myelin antigens, produce bystander suppression, antiinflammatory effects, and neuroprotection. (C) 2003 Elsevier Science Inc. All rights reserved.