Myasthenia Gravis: Bridging Pathophysiology with Precision and Targeted Therapies

Abstract

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder characterized by fluctuating skeletal muscle weakness resulting from impaired neuromuscular transmission. The condition is primarily mediated by autoantibodies directed against postsynaptic components, particularly acetylcholine receptors (AChRs), muscle-specific kinase (MuSK), and lipoprotein receptor-related protein 4 (LRP4). These antibodies lead to complement-mediated damage, receptor degradation, and structural alterations at the neuromuscular junction. MG exhibits a bimodal age distribution, affecting younger females and older males, and is frequently associated with thymic abnormalities such as thymic hyperplasia and thymoma. Clinically, the disease presents with ocular manifestations including ptosis and diplopia, along with generalized weakness involving bulbar, limb, and respiratory muscles. Diagnosis is based on serological detection of autoantibodies, electrophysiological studies, and imaging techniques to evaluate thymic pathology. Current management strategies focus on symptomatic relief and immunomodulation, including acetylcholinesterase inhibitors, corticosteroids, immunosuppressive agents, and thymectomy. Advanced therapies such as monoclonal antibodies targeting B cells and complement pathways have significantly improved clinical outcomes in refractory cases. Emerging therapeutic approaches, including FcRn inhibitors, gene therapy, and targeted biologics, offer promising avenues for more effective and personalized treatment. This review provides a comprehensive overview of the pathophysiology, clinical features, diagnostic strategies, and therapeutic developments in myasthenia gravis, highlighting recent progress and future directions aimed at improving patient care and quality of life.