Complement C3 inhibitory peptide AMY-101 ameliorates brain injury in a mouse model of NMOSD

Background Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease of the central nervous system, clinically characterized primarily by optic neuritis and transverse myelitis. This study aimed to investigate the therapeutic potential of the complement C3 inhibitory peptide AMY-101 in experimental models of NMOSD.Methods In vitro experiments were performed using AQP4-transfected cells exposed to AQP4-IgG and human complement to assess complement-dependent cytotoxicity and membrane attack complex (MAC) deposition. In vivo efficacy was evaluated in an intracerebral injection mouse model of NMOSD, in which histopathological changes after AMY-101 treatment were compared with those in untreated controls.Results AMY-101 significantly attenuated AQP4-IgG– and complement-mediated cytotoxicity and inhibited MAC formation in vitro. In the NMOSD mouse model, AMY-101 treatment markedly reduced astrocyte loss, AQP4 depletion, and demyelination compared with controls.Conclusion These findings demonstrate that complement C3 inhibition with AMY-101 effectively ameliorates key pathological features of NMOSD in experimental models, supporting its potential as a therapeutic strategy and providing a rationale for further preclinical and clinical investigation.