Aquaporin 4 and neuromyelitis optica.
Aquaporin 4 and neuromyelitis optica.
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DOI：
10.1016/s1474-4422(12)70133-3
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发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
Verkman AS
中科院分区：
文献类型：
--
作者：
Papadopoulos MC;Verkman AS
视神经脊髓炎是一种中枢神经系统炎症性脱髓鞘疾病。针对星形胶质细胞水通道蛋白AQP4(AQP4)的循环IgG1抗体的发现，以及AQP4-Ig G参与视神经脊髓炎发病的证据，彻底改变了我们对该疾病的认识。然而，重要的问题仍然悬而未决--例如，我们不知道AQP4-IgG阴性疾病的原因，星形胶质细胞损伤如何导致脱髓鞘，T细胞的作用，为什么表达AQP4的外周器官没有受损，循环中的AQP4-Ig G如何进入视神经脊髓炎病变。出现了新的候选药物，如水通道单抗(AQP4-Ig G结合的非致病抗体阻滞剂)、西维来司(中性粒细胞弹性蛋白酶抑制剂)和eculizumab(补体抑制剂)。尽管进展迅速，但由于患有这种疾病的人数很少，测试新药的随机临床试验将是具有挑战性的。
Neuromyelitis optica is an inflammatory demyelinating disorder of the CNS. The discovery of circulating IgG1 antibodies against the astrocyte water channel protein aquaporin 4 (AQP4) and the evidence that AQP4-IgG is involved in the development of neuromyelitis optica revolutionised our understanding of the disease. However, important unanswered questions remain—for example, we do not know the cause of AQP4-IgG-negative disease, how astrocyte damage causes demyelination, the role of T cells, why peripheral AQP4-expressing organs are undamaged, and how circulating AQP4-IgG enters neuromyelitis optica lesions. New drug candidates have emerged, such as aquaporumab (non-pathogenic antibody blocker of AQP4-IgG binding), sivelestat (neutrophil elastase inhibitor), and eculizumab (complement inhibitor). Despite rapid progress, randomised clinical trials to test new drugs will be challenging because of the small number of individuals with the disorder.