Specific vaccines against autoimmune diseases

Copolymer 1 (Cop 1, Copaxone) is a synthetic amino acid copolymer effective in suppression of experimental allergic encephalomyelitis (EAE). The suppr essive effect of Cop 1 in EAE is not restricted to a certain species, disea se type or encephalitogen used for EAE induction. In phase II and III clini cal trials, Cop 1 was found to slow the progression of disability and reduc e the relapse rate in exacerbating-remitting multiple sclerosis (MS) patien ts. In vivo and in vitro studies suggest that the mechanism for Cop 1 activ ity in EAE and MS involves, as an initial step, the binding of Cop 1 to MHC class II molecules. This binding results in competition with myelin antige ns for T-cell activation, both at the MHC and T-cell receptor levels and in induction of specific suppressor cells of the Th2 type. As an antigen-spec ific intervention, Cop 1 has the advantage of reduced probability for long- term damage to the immune system, and is thus a safe and effective novel th erapeutic approach to MS. It also serves to illustrate the new concept of a drug/vaccine specific for a single autoimmune disease. Indeed, we have use d a similar approach for myasthenia gravis. Myasthenia gravis (MG) and its experimental animal model, experimental autoimmune MG (EAMG), are immune di sorders characterized by circulating antibodies and lymphocyte autoreactivi ty to nicotinic acetylcholine receptor (AChR). We utilized peptides represe nting different sequences of the human acetylcholine receptor alpha-subunit to study the role of T cells in the initiation, development and immunomodu laton of myasthenia gravis. Here we summarize our studies over the last dec ade on T cells specific to 'myasthenogenic' epitopes of the alpha-subunit o f the human acetylcholine receptor and their relevance for myasthenia gravi s. (C) 1999 Academie des sciences/Editions scientifiques et medicales Elsev ier SAS.