Modeling myasthenia gravis with an optogenetic neuromuscular platform: evaluation of a new drug
Embargo Date
2025-02-06
OA Version
Citation
Abstract
Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness caused by deterioration of the neuromuscular junction (NMJ). MG autoantibodies typically target acetylcholine receptor (AChR) proteins in the NMJ, blocking their function, causing their internalization and turnover, or damaging the cell through the complement protein cascade. The purpose of this study is to recapitulate the pathophysiology of MG using an in vitro human 3D optogenetic NMJ model, evaluate functional changes due to MG patient serum, and to test the efficacy of a complement protein inhibitor. Understanding the morphological and functional changes caused by various patient sera and their antibodies will assist in evaluating the inhibitor and help design future treatments for MG. This study showed that MG patient sera decreased NMJ function significantly in the model and demonstrated that the complement inhibitor was effective at protecting NMJ function when used prophylactically.
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License
Attribution 4.0 International