Glatiramer acetate in the treatment of multiple sclerosis

Abstract

The development of glatiramer acetate (GA) was a result of the juxtaposition of unexpected serendipity with rigorous scientific investigation. Experimental autoimmune encephalomyelitis (EAE) has long served as an animal model for multiple sclerosis (MS). This inflammatory disease can be induced with injection of whole spinal cord homogenate or specific proteins, including myelin basic protein (MBP), proteolipid protein, or myelin oligodendrocyte glycoprotein. In the early 1960s, investigators at the Weitzmann Institute in Israel sought to generate a polymer that would reproduce the effects of MBP in eliciting EAE. They believed that development of a synthetic molecule that could mimic the encephalitogenic effects of EAE might provide a useful tool for further investigation of that animal model. Among the many polymers they produced, one, in particular, failed to produce EAE. Surprisingly, this compound, then referred to as copolymer 1 (Cop 1), prevented and suppressed EAE [1]. Initial experiments demonstrated a markedly suppressive effect on EAE in rabbits and guinea pigs induced with bovine and human MBP [2]. The incidence of EAE decreased from approximately 75% in the control group to approximately 20% in the Cop 1–treated animals. EAE is species specific regarding the species from which the MBP is derived and the species in which the disease is induced. Thus, the next logical step was to investigate the effects of Cop 1 in other species. The originally unexpected outcome of suppression of EAE was recapitulated in a variety of animal species, including mice [3] and subhuman primates. The experimental work in rhesus monkeys [4] and baboons [5] particularly was encouraging. In these species, MBP-induced EAE is highly lethal. Yet, administration of Cop 1 was able to reverse the condition even after symptoms had appeared, a situation