Prevention of Anti-HMGCR Immune-Mediated Necrotising Myopathy by C5 Complement Inhibition in a Humanised Mouse Model.

ABSTRACT: Introduction: immune-mediated necrotising myopathy (IMNM) is associated with pathogenic anti-signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies, at least partly through activation of the classical pathway of the complement. We evaluated zilucoplan, an investigational drug, and a macrocyclic peptide inhibitor of complement component 5 (C5), in humanized mouse models of IMNM. Methods: purified immunoglobulin G (IgG) from an anti-HMGCR⁺ IMNM patient was co-injected intraperitoneally with human complement in C57BL/6, C5-deficient B10 (C5^def) and Rag2 deficient (Rag2^-/-) mice. Zilucoplan was administered subcutaneously in a preventive or interventional paradigm, either injected daily throughout the dura

SUBMITTER: Julien S 

PROVIDER: S-EPMC9405589 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature