Copolymer-1.

Abstract

Copolymer 1 (Cop-1) is a mixture of synthetic polypeptides composed of four amino acids. Cop-1 was very effective in suppression of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). Two principal mechanisms have been proposed to explain the suppressive activity of Cop-1 in EAE and in multiple sclerosis (MS): the induction of antigen-specific suppressor T cells and the interference with T-cell activation by competition with myelin antigens in binding to the major histocompatibility complex class II molecules. Clinical trials with Cop-1 have demonstrated that Cop-1 positively alters the course of relapsing-remitting multiple sclerosis (MS) by both reducing the relapse rate and slowing the progression of disability. In a 2-year multi-centre, randomized, double-blind, placebo-controlled trial of 251 patients, Cop-1 was shown to reduce relapses by an average of 29% when compared with placebo. A preliminary study on patients with relapsing-remitting MS treated with Cop-1 showed a reduced number of new enhancing lesions on MRI as well as a reduced accumulation of lesion load during Cop-1 treatment. Antibodies to copolymer-1, which are found during Cop-1 treatment, do not interfere with its clinical effects. The side effects of Cop-1 are minimal and acceptable. In vitro and in vivo animal studies have shown a very good safety profile of Cop-1 which is devoid of teratogenic or mutagenic effects. Cop-1 joins interferon beta as a good candidate for treatment of relapsing-remitting MS.