Regulation of Neuromyelitis Optica via Tolerance Induced by PLG Nanoparticles Encapsulating Aquaporin 4 Epitopes

AQP4 is a devastating autoimmune demyelinating disease of the spinal cord and optic nerve mediated by T cell and antibody responses to aquaporin-4 (AQP4). In this exploratory high-risk high-reward project, we will establish reliable mouse models of NMO on both the C57BL/6 and SJL/J genetic backgrounds and test the efficacy and mechanisms of tolerance induced by the i.v. infusion of biodegradable PLG nanoparticles encapsulating recombinant AQP4 or the immunodominant AQP4 peptides to treat clinical disease and the accompanying AQP4-specific immune responses. It is hoped that the successful execution of these exploratory studies will propel the rapid clinical testing of this novel nanoparticle-based immune tolerance approach, currently in a phase 2 trial in celiac disease, which specifically targets the underlying cause of disease in NMO patients.