Myasthenia gravis: innovative therapies and new frontiers in research

Myasthenia gravis (MG) is a rare acquired autoimmune disease affecting the neuromuscular junction, characterized by fluctuating muscle weakness that worsens with activity and improves with rest. The disease predominantly affects ocular, bulbar, neck, and limb muscles, with a prevalence of 1/5000 and incidence of 1/250,000–1/33,000 in Europe. Pathogenesis involves autoantibodies targeting post-synaptic membrane antigens, primarily acetylcholine receptors (AChR-Ab+, 80–90% of cases) or muscle-specific tyrosine kinase (MuSK-Ab+, 5–6% of cases). Current therapeutic approaches include symptomatic treatment with acetylcholinesterase inhibitors, immunosuppressive therapy with corticosteroids and non-steroidal immunosuppressants, and rescue therapies such as plasmapheresis for myasthenic crises. Approximately 5% of patients develop refractory MG, requiring targeted biological therapies including complement inhibitors (eculizumab, ravulizumab, zilucoplan) and neonatal Fc receptor (FcRn) inhibitors (efgartigimod alfa, rozanolixizumab). Recent clinical trials have demonstrated the efficacy of nipocalimab, a novel FcRn inhibitor, which recently received Food and Drug Administration (FDA) approval. Emerging chimeric antigen receptor (CAR)-T cell therapies targeting CD19-positive B cells represent an innovative approach inspired by oncological applications, with ongoing phase I/II studies (RESET-MG, KYSA-6) showing promising preliminary results in refractory cases. This review provides a comprehensive analysis of current therapeutic strategies, novel biological agents, and innovative cell-based therapies, highlighting the evolving therapeutic landscape of MG management.