PROJECT SUMMARY/ABSTRACT Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOGAD) is a rare disease characterized as a neurological, inflammatory, demyelinating disorder of the central nervous system. The symptoms of MOGAD include vision loss, symptoms associated with damage to the spinal cord, as well as seizures. While the current standard of care against MOGAD includes steroids and immunosuppressants, they are associated with systemic immunosuppression with complications and frequent debilitating relapses. Thus, there is an urgent need for new targeted treatment options for MOGAD patients. As MOG is the sole target antigen in MOGAD patients, MOG is an attractive target. Here, we propose to develop a novel nanoparticle platform for the treatment of MOGAD. Toward this goal, we have developed synthetic high-density lipoprotein NanoDiscs for efficient delivery of antigen peptides to lymph nodes. Our preliminary data shows that NanoDiscs induce robust antigen-specific immune tolerance and disease modification in murine models of experimental autoimmune encephalomyelitis (EAE) and another autoimmune disorder, type 1 diabetes (T1D). Based on our compelling proof-of-concept data, here we propose to further develop NanoDiscs for the treatment of MOGAD.