Novel treatment strategies for acetylcholine receptor antibody-positive myasthenia gravis and related disorders

• Published in: Autoimmunity reviews 2022-07, Vol.21 (7), p.103104, Article 103104
• Main Authors: Mané-Damas, Marina, Molenaar, Peter C., Ulrichts, Peter, Marcuse, Florit, De Baets, Marc H., Martinez-Martinez, Pilar, Losen, Mario
• Format: Article
• Language: English
• Subjects: Autoantibodies; Myasthenia gravis; Neuromuscular transmission; Novel therapies; Plasma cells; Thymectomy
• ISSN: 1568-9972; 1568-9972
• DOI: 10.1016/j.autrev.2022.103104

The presence of autoantibodies directed against the muscle nicotinic acetylcholine receptor (AChR) is the most common cause of myasthenia gravis (MG). These antibodies damage the postsynaptic membrane of the neuromuscular junction and cause muscle weakness by depleting AChRs and thus impairing synaptic transmission. As one of the best-characterized antibody-mediated autoimmune diseases, AChR-MG has often served as a reference model for other autoimmune disorders. Classical pharmacological treatments, including broad-spectrum immunosuppressive drugs, are effective in many patients. However, complete remission cannot be achieved in all patients, and 10% of patients do not respond to currently used therapies. This may be attributed to production of autoantibodies by long-lived plasma cells which are resistant to conventional immunosuppressive drugs. Hence, novel therapies specifically targeting plasma cells might be a suitable therapeutic approach for selected patients. Additionally, in order to reduce side effects of broad-spectrum immunosuppression, targeted immunotherapies and symptomatic treatments will be required. This review presents established therapies as well as novel therapeutic approaches for MG and related conditions, with a focus on AChR-MG. •Myasthenia gravis (MG) is a well-understood antibody-mediated autoimmune disorder that generally responds well to broad-spectrum immunosuppressive drugs•Conventional treatments cause severe side effects in 30%, and are ineffective in 10% of, MG patients•Innovative treatment-strategies for MG utilize competitor antibodies, complement inhibitors, FcRn antagonists and drugs targeting antibody secreting cells•A substantial number of clinical trials to investigate the potential benefit of innovative therapies for MG are ongoing•Analysis of immune cells from individual MG patients is useful for the identification of effective personalized treatments