[Pubmed] Targeting Autoimmunity in Myasthenia Gravis: From Conventional to Novel Therapeutic Approaches

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Protein Pept Lett. 2026 Mar 26. doi: 10.2174/0109298665429857260206223221. Online ahead of print.

ABSTRACT

Myasthenia Gravis is a chronic autoimmune neuromuscular disorder characterized by fluctuating skeletal muscle weakness, most commonly involving ocular, bulbar, respiratory, and limb muscles. This weakness stems from autoantibodies, predominantly immunoglobulin G, against neuromuscular junction components such as acetylcholine receptors or muscle-specific kinase, which ultimately reduces synaptic transmission. MG causes a severe functional impact on normal patients, which often contributes to the reduced quality of life and life-threatening myasthenic crises. This article provides an extensive review of MG's immunopathogenesis with a focus on T and B lymphocytes, pro-inflammatory cytokine involvement, and the components of the complement cascade. Humoral and innate immune mechanisms cooperate and indirectly result from antibodies and continued neuromuscular dysfunction. Clinical MG approval usually depends on a combination of a clinical approach to testing antibodies, electrophysiological technique trials, and, if necessary, imaging methods for thymoma or thymic fusion abnormalities. Regular MG treatment involves acetylcholinesterase inhibitors, corticosteroids, and steroid-sparing immunosuppressant agents (e.g., azathioprine, mycophenolate mofetil). Rapid treatment of MG exacerbations necessitates a process of rapid immunomodulation, including plasma exchanges and intravenous immunoglobulin to rapidly reduce reversed autoantibodies. Novel drug discovery is aimed at targeted immunomodulation, including clinical application of inhibitors of the complement C5 (eculizumab, ravulizumab, zilucoplan), type I neonatal Fc receptor antagonists (efgartigimod, rozanolixizumab), BTK inhibitors, B-cell-directed monoclonal antibodies, and new dendritic cell T cell antireceptor constructs. They can carve out paradigm shifts as these novel resourcing solutions and therapeutic options allow precision medicine to individual immunopathogenic profiles. Synergistic combinations of conventional and modern medicine are a promising comprehensive strategy for MG patients. Reappraisal driven by the biological mechanism, three may deliver better long-term functional outcomes and quality of life.

PMID:41928685 | DOI:10.2174/0109298665429857260206223221


Source: https://pubmed.ncbi.nlm.nih.gov/4192868 ... t6+133c1fe