New therapies for autoimmune myasthenia gravis

Myasthenia gravis is a rare, chronic autoimmune disease of the neuromuscular junction that is characterised by muscle weakness. Most people with the disease have antibodies against one of the transmembrane proteins at the synapse, such as the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK). Activation of complement by AChR antibodies is thought to be one of the key pathogenic mechanisms for autoimmune myasthenia gravis. 1 Mantegazza R Bernasconi P Cavalcante P Myasthenia gravis: from autoantibodies to therapy. Curr Opin Neurol. 2018; 31: 517-525 Crossref PubMed Scopus (38) Google Scholar Complement inhibition—in particular of component 5 (C5)—prevents formation of the membrane attack complex, subsequently limiting the capacity of AChR antibodies to damage the postsynaptic muscle membrane, and helping the muscle to withstand the autoantibody attack. Another potential therapeutic target in autoimmune myasthenia gravis is the neonatal Fc receptor (FcRn), which plays a part in the transfer of maternal IgGs to neonates as well as trafficking IgGs and albumin into recycling pathways through vascular endothelial cells. 2 Roopenian DC Akilesh S FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. 2007; 7: 715-725 Crossref PubMed Scopus (1644) Google Scholar Blocking of FcRn might reduce overall levels of IgG and pathogenic autoantibodies. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 studyRozanolixizumab showed clinically meaningful improvements in patient-reported and investigator-assessed outcomes in patients with generalised myasthenia gravis, for both 7 mg/kg and 10 mg/kg doses. Both doses were generally well tolerated. These findings support the mechanism of action of neonatal Fc receptor inhibition in generalised myasthenia gravis. Rozanolixizumab represents a potential additional treatment option for patients with generalised myasthenia gravis. Full-Text PDF Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 studyZilucoplan treatment showed rapid and clinically meaningful improvements in myasthenia gravis-specific efficacy outcomes, had a favourable safety profile, and was well tolerated, with no major safety findings. Zilucoplan is a new potential treatment option for a broad population of patients with AChR-positive generalised myasthenia gravis. The long-term safety and efficacy of zilucoplan is being assessed in an ongoing open-label extension study. Full-Text PDF Correction to Lancet Neurol 2023; 22: 368–69Verschuuren J. New therapies for autoimmune myasthenia gravis. Lancet Neurol 2023; 22: 368–69—In this Comment, the drug rozanolixizumab was misspelled twice. This correction has been made to the online version as of May 18, 2023. Full-Text PDF