英国牛津大学Robert E. MacLaren小组揭示了RPGR突变引起的X连锁色素性视网膜炎（RP）的人类首次基因治疗试验的初步结果。该研究成果在线发表在2020年2月24日的《自然—医学》上。

研究人员对18位X连锁RP患者进行了长达6个月的人类首次1/2期剂量递增临床试验（https://clinicaltrials.gov/：NCT03116113）。X连锁RP是由RP GTPase调节基因（RPGR）基因突变引起的。

该研究的主要参数是安全性，次要参数包括视敏度、显微视野检查和视网膜中央厚度。在视网膜下利用腺病毒载体表达密码子优化的人RPGR（AAV8-coRPGR）基因，除了高剂量类固醇反应性视网膜下炎症的患者外，其他并没有产生安全性方面的问题，并达到了预先设定的临床效果。

对6例患者进行跟踪，研究人员发现从1个月开始病人的视野得到改善，并一直维持到随访的最后时刻。

研究人员表示，视网膜基因疗法在治疗色素性视网膜炎中具有广阔的前景，RP主要是由光感受器变性造成的，可导致年轻人严重视力丧失。

附：英文原文

Title: Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR

Author: Jasmina Cehajic-Kapetanovic, Kanmin Xue, Cristina Martinez-Fernandez de la Camara, Anika Nanda, Alexandra Davies, Laura J. Wood, Anna Paola Salvetti, M. Dominik Fischer, James W. Aylward, Alun R. Barnard, Jasleen K. Jolly, Edmond Luo, Brandon J. Lujan, Tuyen Ong, Aniz Girach, Graeme C. M. Black, Ninel Z. Gregori, Janet L. Davis, Potyra R. Rosa, Andrew J. Lotery, Byron L. Lam, Paulo E. Stanga, Robert E. MacLaren

Issue&Volume: 2020-02-24

Abstract: Retinal gene therapy has shown great promise in treating retinitis pigmentosa (RP), a primary photoreceptor degeneration that leads to severe sight loss in young people. In the present study, we report the first-in-human phase 1/2, dose-escalation clinical trial for X-linked RP caused by mutations in the RP GTPase regulator (RPGR) gene in 18 patients over up to 6months of follow-up (https://clinicaltrials.gov/: NCT03116113). The primary outcome of the study was safety, and secondary outcomes included visual acuity, microperimetry and central retinal thickness. Apart from steroid-responsive subretinal inflammation in patients at the higher doses, there were no notable safety concerns after subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8-coRPGR), meeting the pre-specified primary endpoint. Visual field improvements beginning at 1month and maintained to the last point of follow-up were observed in six patients.

DOI: 10.1038/s41591-020-0763-1

Source: https://www.nature.com/articles/s41591-020-0763-1