Departments of Medicine and Physiology, University of California, San Francisco, CA, USA.
Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Expert Opin Ther Targets. 2020 Mar;24(3):219-229. doi: 10.1080/14728222.2020.1732927. Epub 2020 Mar 2.
: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system affecting primarily the spinal cord and optic nerves. Most NMOSD patients are seropositive for immunoglobulin G autoantibodies against astrocyte water channel aquaporin-4, called AQP4-IgG, which cause astrocyte injury leading to demyelination and neurological impairment. Current therapy for AQP4-IgG seropositive NMOSD includes immunosuppression, B cell depletion, and plasma exchange. Newer therapies target complement, CD19 and IL-6 receptors.: This review covers early-stage pre-clinical therapeutic approaches for seropositive NMOSD. Targets include pathogenic AQP4-IgG autoantibodies and their binding to AQP4, complement-dependent and cell-mediated cytotoxicity, blood-brain barrier, remyelination and immune effector and regulatory cells, with treatment modalities including small molecules, biologics, and cells.: Though newer NMOSD therapies appear to have increased efficacy in reducing relapse rate and neurological deficit, increasingly targeted therapies could benefit NMOSD patients with ongoing relapses and could potentially be superior in efficacy and safety. Of the various early-stage therapeutic approaches, IgG inactivating enzymes, aquaporumab blocking antibodies, drugs targeting early components of the classical complement system, complement regulator-targeted drugs, and Fc-based multimers are of interest. Curative strategies, perhaps involving AQP4 tolerization, remain intriguing future possibilities.
视神经脊髓炎谱系疾病（NMOSD）是一种影响中枢神经系统的炎症性脱髓鞘疾病，主要影响脊髓和视神经。大多数 NMOSD 患者血清中存在针对水通道蛋白 4（AQP4）的免疫球蛋白 G 自身抗体，称为 AQP4-IgG，它导致星形胶质细胞损伤，从而导致脱髓鞘和神经功能损伤。目前针对 AQP4-IgG 阳性 NMOSD 的治疗包括免疫抑制、B 细胞耗竭和血浆置换。较新的治疗方法针对补体、CD19 和 IL-6 受体。
本文综述了针对 NMOSD 血清阳性患者的早期临床前治疗方法。靶标包括致病性 AQP4-IgG 自身抗体及其与 AQP4 的结合、补体依赖性和细胞介导的细胞毒性、血脑屏障、髓鞘再生以及免疫效应细胞和调节细胞，治疗方式包括小分子、生物制剂和细胞。
虽然新型 NMOSD 治疗方法似乎在降低复发率和神经功能缺损方面具有更高的疗效，但针对不断复发的 NMOSD 患者的靶向治疗可能会更有效，并且在疗效和安全性方面可能具有优势。在各种早期治疗方法中，IgG 失活酶、AQP4 阻断抗体、针对经典补体系统早期成分的药物、补体调节剂靶向药物和基于 Fc 的多聚体具有研究前景。或许涉及 AQP4 耐受的治愈策略仍是未来的诱人可能性。
