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Myasthenia gravis: the changing treatment landscape in the era of molecular therapies

Nature Reviews Neurology volume 20, pages 84–98 (2024)Cite this article

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Abstract

Myasthenia gravis (MG) is an autoimmune disorder that affects the neuromuscular junction, leading to muscle weakness and fatigue. MG is caused by antibodies against the acetylcholine receptor (AChR), the muscle-specific kinase (MuSK) or other AChR-related proteins that are expressed in the postsynaptic muscle membrane. The standard therapeutic approach for MG has relied on acetylcholinesterase inhibitors, corticosteroids and immunosuppressants, which have shown good efficacy in improving MG-related symptoms in most people with the disease; however, these therapies can carry a considerable burden of long-term adverse effects. Moreover, up to 15% of individuals with MG exhibit limited or no response to these standard therapies. The emergence of molecular therapies, including monoclonal antibodies, B cell-depleting agents and chimeric antigen receptor T cell-based therapies, has the potential to revolutionize the MG treatment landscape. This Review provides a comprehensive overview of the progress achieved in molecular therapies for MG associated with AChR antibodies and MuSK antibodies, elucidating both the challenges and the opportunities these therapies present to the field. The latest developments in MG treatment are described, exploring the potential for personalized medicine approaches.

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Fig. 1: Immunopathogenesis of AChR-MG and MuSK-MG, and therapeutic targets.
Fig. 2: Standard therapy algorithm for the management of AChR-MG and MuSK-MG.
Fig. 3: An algorithm for the management of AChR-MG and MuSK-MG incorporating new molecular therapies.

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  1. Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy

    Raffaele Iorio

  2. Neurology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Raffaele Iorio

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Iorio, R. Myasthenia gravis: the changing treatment landscape in the era of molecular therapies. Nat Rev Neurol 20, 84–98 (2024). https://doi.org/10.1038/s41582-023-00916-w

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