New research from the Myasthenia Gravis Rare Disease Network (MGNet). This summary is based on a paper published in the journal Proceedings of the National Academy of Sciences of the United States of America on October 21, 2025, titled "Therapeutic IgG- and IgM-specific proteases disarm the acetylcholine receptor autoantibodies that drive myasthenia gravis pathology."
Read the paper here.
Learn more about MGNet.
Transcript:
New research from the Myasthenia Gravis Rare Disease Network (MGNet), a research group of the Rare Diseases Clinical Research Network.
Evaluating the Therapeutic Potential of Immunoglobin G- and Immunoglobin M-Specific Proteases in Acetylcholine Receptor-Positive Myasthenia Gravis.
This summary is based on a paper published in the journal Proceedings of the National Academy of Sciences of the United States of America on October 21, 2025.
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder in which antibodies targeting the acetylcholine receptor (AChR) cause muscle weakness. Current therapies help many patients, but some remain refractory, underscoring the need for more personalized approaches.
In this study, researchers evaluated the therapeutic potential of S-1117, a pan-IgG–specific protease engineered to selectively cleave the Fcγ region of pathogenic AChR-IgG. Using live cell-based assays with monoclonal autoantibodies and patient serum, the team showed that S-1117 effectively impaired IgG-mediated complement activation on AChR-expressing cells.
Importantly, the work uncovered a previously unrecognized MG subset driven by pathogenic AChR-IgM, which either amplified IgG-mediated injury or served as the primary source of complement activation. An IgM-specific protease fully suppressed IgM-driven pathogenicity, and combining IgG- and IgM-targeted enzymes achieved broader inhibition.
These findings reveal critical disease heterogeneity in MG and highlight Ig-specific proteases as a promising precision-medicine strategy to improve treatment for patients with antibody-mediated weakness.
Read the paper here.
Learn more about MGNet.
Transcript:
New research from the Myasthenia Gravis Rare Disease Network (MGNet), a research group of the Rare Diseases Clinical Research Network.
Evaluating the Therapeutic Potential of Immunoglobin G- and Immunoglobin M-Specific Proteases in Acetylcholine Receptor-Positive Myasthenia Gravis.
This summary is based on a paper published in the journal Proceedings of the National Academy of Sciences of the United States of America on October 21, 2025.
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder in which antibodies targeting the acetylcholine receptor (AChR) cause muscle weakness. Current therapies help many patients, but some remain refractory, underscoring the need for more personalized approaches.
In this study, researchers evaluated the therapeutic potential of S-1117, a pan-IgG–specific protease engineered to selectively cleave the Fcγ region of pathogenic AChR-IgG. Using live cell-based assays with monoclonal autoantibodies and patient serum, the team showed that S-1117 effectively impaired IgG-mediated complement activation on AChR-expressing cells.
Importantly, the work uncovered a previously unrecognized MG subset driven by pathogenic AChR-IgM, which either amplified IgG-mediated injury or served as the primary source of complement activation. An IgM-specific protease fully suppressed IgM-driven pathogenicity, and combining IgG- and IgM-targeted enzymes achieved broader inhibition.
These findings reveal critical disease heterogeneity in MG and highlight Ig-specific proteases as a promising precision-medicine strategy to improve treatment for patients with antibody-mediated weakness.
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