Novel therapies for myasthenia gravis: Translational research from animal models to clinical application
May 2026
Abstract
Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial long-term side effects associated with standard treatments (including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.
Introduction
Myasthenia gravis (MG) is a rare chronic autoimmune condition that affects the postsynaptic neuromuscular junction (NMJ). The overall prevalence of MG is estimated to be between 150 and 250 cases per million individuals, with an annual incidence of 8 to 10 cases per million person/year. MG is more common in women under 40 years of age and men over 60, and its incidence appears to increase with age (Gilhus et al., 2019). The predominant clinical manifestation is muscle fatigability, typically fluctuating over time, variably affecting the ocular, bulbar, respiratory, and limb skeletal muscles (Gilhus et al., 2019). Approximately 15% of MG cases remain limited to the ocular muscles, but most patients eventually progress to generalized MG (gMG), involving multiple muscle groups. Most gMG patients have detectable pathogenic antibodies in their serum, with around 85% testing positive for anti-acetylcholine receptor (AChR) antibodies while a smaller percentage has antibodies against muscle-specific kinase (MuSK) or lipoprotein receptor-related protein 4 (LRP4). 10%–15% of patients have no detectable antibodies and are therefore classified as seronegative.
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