重视自然病程研究,科学开展遗传性视网膜疾病的基因治疗  

Paying attention to the natural course of disease for a development of gene therapy of inherited retinal diseases

作　　者：汪枫桦[1] 陈洁琼 孙晓东[1] Wang Fenghua;Chen Jieqiong;Sun Xiaodong(Department of Ophthalmology,Shanghai General Hospital,Shanghai Engineering Center for Visual Science and Photomedicine,Shanghai 200080,China)

机构地区：[1]上海交通大学附属第一人民医院眼科,上海眼视觉与光医学工程技术研究中心,200080

出　　处：《中华实验眼科杂志》2021年第8期665-669,共5页Chinese Journal Of Experimental Ophthalmology

基　　金：“重大新药创制”科技重大专项课题项目(2019ZX09301113);上海交通大学医学院多中心临床研究项目(DLY201813)。

摘　　要：多数遗传性视网膜疾病(IRDs)可造成永久性视功能严重损害且缺乏有效的治疗方法。2017年全球首个IRDs的基因治疗药物Luxturna获得美国FDA批准,为该类疾病的治疗带来了新的希望。IRDs发病早、患者数量相对少,以往对自然病程的认识有限。IRDs的基因治疗研究必须基于对疾病发病机制、自然病程的深入认识,对基因疗法实施最佳“治疗窗”的选择是治疗成功的前提。目前,用于基因治疗的主要基因传递载体为重组病毒载体,其组织免疫原性、成瘤性及其与宿主细胞整合的安全性和有效性决定了治疗的结局,故亟待建立IRDs基因疗法的临床评价技术。眼科疾病的基因疗法还涉及法律法规、伦理道德、产品流程、人种和地域环境、疾病进展过程、基因突变种类、患者获益和风险比等多种因素的考量。因此,充分考虑IRDs人群的需求,尤其是儿童患者的特殊性,积极开展我国IRDs的自然病程研究,对于科学、规范地开展基因治疗临床试验、有效确立基因治疗临床研究的终点结局指标、遵循国际规范的伦理准则都具有重要意义。Most inherited retinal diseases(IRDs)severely impair vision and lack effective treatments.With the approval of Luxturna,the world's first gene therapy drug for IRDs in 2017 by the U.S.FDA,gene therapy has brought new hope for the treatment of the disease.With an early onset and a relatively small number of patients,the understanding of the natural course of IRDs is limited in the past.The research on gene therapy of IRDs is mainly based on the in-depth understanding of the pathogenesis and natural course of disease,and the selection of the optimal treatment window for the implementation of gene therapy is the premise of successful treatment.At the same time,the main vector for gene therapy is recombinant virus vector,and its tissue-immunogenicity,tumorigenicity,safety of its integration with host cells and effectiveness determine the outcome of therapy,so the evaluation technology of IRDs gene therapy needs to be established.Gene therapy for ophthalmic diseases also involves the consideration of laws and regulations,ethics,product process,races and regional environment,disease progression,gene mutation types,patient benefit and risk ratio,and other factors.Therefore,it is of great significance to take full account of the differences in IRDs population,especially the particularity of children patients,and actively carry out the study on the natural course of IRDs in China for the scientific and normative development of clinical trials of gene therapy,the effective establishment of endpoint and outcome indicators for clinical studies of gene therapy,and the compliance with international norms of ethics.

关 键 词：基因疗法 遗传性视网膜疾病 自然病程 病毒载体 伦理 

分 类 号：R774.1[医药卫生—眼科]