Structure-Based Approaches to Antigen-Specific Therapy of Myasthenia Gravis

Abstract

A majority of Myasthenia Gravis (MG) cases (~85%) are caused by pathological autoimmune antibodies to muscle nicotinic acetylcholine receptors (nAChRs). An attractive approach to treating MG is therefore blocking the binding of autoimmune antibodies to nAChR, or removing specifically nAChR antibodies, or selectively inhibiting and eliminating nAChR-specific B cells. This chapter will review highresolution structural studies of muscle nAChR and its complexes with antibodies derived from experimental autoimmune Myasthenia Gravis (EAMG). Based on these structural analyses, various strategies, including using small molecules to block the binding of MG autoimmune antibodies, and engineered chimeric nAChR antigen to specifically target and eliminate B cells that produce nAChR-specific antibodies, will be discussed.