Novel immunotherapy against MOG antibody disease

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PROJECT SUMMARY/ABSTRACT Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOGAD) is a rare, neurological, immune- mediated 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 for immunotherapy against MOGAD. Here, we propose to develop a novel strategy for immunotherapy against MOG. Toward this goal, we have developed synthetic high-density lipoprotein NanoDiscs that are particularly well suited for lymph node targeting. We have shown that NanoDiscs carrying antigens induce robust CD4 regulatory T cells and downregulate autoantibodies, thereby leading to antigen- specific immune tolerance in a murine model of experimental autoimmune encephalomyelitis. Based on our compelling proof-of-concept data, here we propose to further develop NanoDiscs carrying human MOG antigens and identify a lead candidate for clinical translation.