Patient-specific therapeutic benefit of MuSK agonist antibody ARGX-119 in MuSK myasthenia gravis passive transfer models.

ABSTRACT: Muscle-specific kinase (MuSK) orchestrates the establishment and maintenance of neuromuscular synapses. Autoantibodies targeting MuSK cause myasthenia gravis (MG), a disease characterized by skeletal muscle weakness. MuSK autoantibodies are predominantly IgG4 which are bispecific, functionally monovalent antibodies that are antagonists of MuSK signaling. We hypothesized that bivalent MuSK agonist antibodies can rescue MuSK MG. Here, we investigated whether ARGX-119, a MuSK frizzled-like domain agonist antibody, can ameliorate disease in passive transfer models induced by polyclonal patient IgG4. ARGX-119 improved survival and muscle weakness in a mouse model induced by one patient material, but not by three others. Patient-specific efficacy could not be explained by titer or competition fo

SUBMITTER: Lim JL 

PROVIDER: S-EPMC11783450 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature