Article ; Online: Discovery of functionally distinct anti-C7 monoclonal antibodies and stratification of anti-nicotinic AChR positive Myasthenia Gravis patients.
2022 Volume 13, Page(s) 968206
Abstract: Myasthenia Gravis (MG) is mediated by autoantibodies against acetylcholine receptors that cause loss of the receptors in the neuromuscular junction. Eculizumab, a C5-inhibitor, is the only approved treatment for MG that mechanistically addresses ... ...
| Abstract | Myasthenia Gravis (MG) is mediated by autoantibodies against acetylcholine receptors that cause loss of the receptors in the neuromuscular junction. Eculizumab, a C5-inhibitor, is the only approved treatment for MG that mechanistically addresses complement-mediated loss of nicotinic acetylcholine receptors. It is an expensive drug and was approved despite missing the primary efficacy endpoint in the Phase 3 REGAIN study. There are two observations to highlight. Firstly, further C5 inhibitors are in clinical development, but other terminal pathway proteins, such as C7, have been relatively understudied as therapeutic targets, despite the potential for lower and less frequent dosing. Secondly, given the known heterogenous mechanisms of action of autoantibodies in MG, effective patient stratification in the REGAIN trial may have provided more favorable efficacy readouts. We investigated C7 as a target and assessed the |
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| MeSH term(s) | Animals ; Antibodies, Monoclonal/metabolism ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents, Immunological ; Autoantibodies/metabolism ; Complement System Proteins/metabolism ; Epitopes ; Humans ; Macaca fascicularis ; Myasthenia Gravis, Autoimmune, Experimental ; Nicotine ; Rats ; Receptors, Cholinergic ; Receptors, Nicotinic |
| Chemical Substances | Antibodies, Monoclonal ; Antineoplastic Agents, Immunological ; Autoantibodies ; Epitopes ; Receptors, Cholinergic ; Receptors, Nicotinic ; Nicotine (6M3C89ZY6R) ; Complement System Proteins (9007-36-7) |
| Language | English |
| Publishing date | 2022-09-05 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2606827-8 |
| ISSN | 1664-3224 ; 1664-3224 |
| ISSN (online) | 1664-3224 |
| ISSN | 1664-3224 |
| DOI | 10.3389/fimmu.2022.968206 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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