Novel immunotherapy against MOG antibody disease

项目摘要/摘要 髓鞘少突胶质细胞糖蛋白(MOG)抗体病(MOGAD)是一种罕见的神经系统、免疫性疾病。 中枢神经系统炎症性脱髓鞘障碍。MOGAD的症状包括 视力丧失，与脊髓损伤相关的症状，以及癫痫发作。虽然现行标准 对MOGAD的护理包括类固醇和免疫抑制剂，它们与系统性 免疫抑制伴随并发症和经常使人衰弱的复发。因此，迫切需要新的 针对MOGAD患者的靶向治疗选择。由于MOG是MOGAD患者的唯一靶抗原，因此MOG是 是抗MOGAD免疫治疗的一个有吸引力的靶点。在这里，我们建议开发一种新的策略来 针对MOG的免疫治疗。为了实现这一目标，我们开发了合成高密度脂蛋白 特别适合于淋巴结靶向的纳米盘。我们已经证明，纳米盘承载着 抗原诱导强大的CD4调节性T细胞并下调自身抗体，从而导致抗原- 实验性自身免疫性脑脊髓炎小鼠模型的特异性免疫耐受。基于我们的 令人信服的概念验证数据，在这里，我们建议进一步开发携带人类MOG抗原的纳米盘 并确定临床翻译的主要候选者。

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.