Copolymer 1 (Cop 1,
Copaxone) is a synthetic
amino acid copolymer effective in suppression of
experimental allergic encephalomyelitis (EAE). The suppressive effect of Cop 1 in EAE is not restricted to a certain species, disease type or encephalitogen used for EAE induction. In phase II and III clinical trials, Cop 1 was found to slow the progression of disability and reduce the relapse rate in exacerbating-remitting
multiple sclerosis (MS) patients. In vivo and in vitro studies suggest that the mechanism for Cop 1 activity 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
antigens 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-specific 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 therapeutic approach to MS. It also serves to illustrate the new concept of a
drug/
vaccine specific for a single
autoimmune disease. Indeed, we have used a similar approach for
myasthenia gravis.
Myasthenia gravis (MG) and its experimental animal model, experimental autoimmune MG (EAMG), are
immune disorders characterized by circulating
antibodies and lymphocyte autoreactivity to
nicotinic acetylcholine receptor (AChR). We utilized
peptides representing different sequences of the human
acetylcholine receptor alpha-subunit to study the role of T cells in the initiation, development and
immunomodulation of
myasthenia gravis. Here we summarize our studies over the last decade on T cells specific to 'myasthenogenic'
epitopes of the alpha-subunit of the human
acetylcholine receptor and their relevance for
myasthenia gravis.