Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
WPI Immunology Frontier Research Center, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Sci Rep. 2018 Jan 8;8(1):34. doi: 10.1038/s41598-017-18362-2.
Neuromyelitis optica (NMO) is an autoimmune disease associated with NMO immunoglobulin G (NMO-IgG), an antibody that selectively binds to the aquaporin-4. Here, we established a localized NMO model by injecting NMO-IgG into the spinal cord, and assessed the efficacy of treating its NMO-like symptoms by blocking repulsive guidance molecule-a (RGMa), an axon growth inhibitor. The model showed pathological features consistent with NMO. Systemic administration of humanized monoclonal anti-RGMa antibody delayed the onset and attenuated the severity of clinical symptoms. Further, it preserved astrocytes and reduced inflammatory-cell infiltration and axonal damage, suggesting that targeting RGMa is effective in treating NMO.
视神经脊髓炎（NMO）是一种自身免疫性疾病，与 NMO 免疫球蛋白 G（NMO-IgG）有关，NMO-IgG 是一种选择性结合水通道蛋白-4 的抗体。在这里，我们通过向脊髓内注射 NMO-IgG 建立了一种局部性 NMO 模型，并评估了通过阻断轴突生长抑制因子 repulsive guidance molecule-a（RGMa）来治疗其类似 NMO 症状的疗效。该模型显示出与 NMO 一致的病理特征。全身性给予人源化单克隆抗 RGMa 抗体可延迟疾病发作并减轻临床症状严重程度。此外，它还能保护星形胶质细胞并减少炎症细胞浸润和轴突损伤，表明靶向 RGMa 治疗 NMO 是有效的。
