Long-term experience with gene augmentation therapy in patients with inherited retinal disease associated with biallelic mutations in RPE65.

IF 1.1 4区生物学

Medizinische Genetik Pub Date : 2025-02-12 eCollection Date: 2025-04-01 DOI:10.1515/medgen-2024-2067

Birgit Lorenz

{"title":"Long-term experience with gene augmentation therapy in patients with inherited retinal disease associated with biallelic mutations in RPE65.","authors":"Birgit Lorenz","doi":"10.1515/medgen-2024-2067","DOIUrl":null,"url":null,"abstract":"RPE65 biallelic mutation-associated inherited retinal degeneration (IRD) is currently the only IRD for which gene therapy is approved. This narrative review provides a brief overview of the disease and an update of the current literature on outcomes following the approval of treatment with voretigene neparvovec (LuxturnaTM) in 2017 (USA) and Europe (2018). Post-marketing results confirm a significant therapeutic effect of this gene augmentation on rod function similar to that seen in the phase 1 to 3 clinical trials. The full-field chromatic light sensitivity test is an appropriate test to demonstrate early and sustained effects of treatment. Visual acuity and visual fields may improve in less advanced disease. Accelerated chorioretinal atrophy (CRA) is a previously unrecognised adverse effect that is now reported in 13 % to 50 % of treated eyes. If central, visual acuity loss and paracentral visual field defects may occur. Further studies are needed to identify patients at risk of CRA in order to maximize patient benefit from a costly intervention.","PeriodicalId":51130,"journal":{"name":"Medizinische Genetik","volume":"37 1","pages":"47-56"},"PeriodicalIF":1.1000,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812477/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medizinische Genetik","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1515/medgen-2024-2067","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

RPE65 biallelic mutation-associated inherited retinal degeneration (IRD) is currently the only IRD for which gene therapy is approved. This narrative review provides a brief overview of the disease and an update of the current literature on outcomes following the approval of treatment with voretigene neparvovec (LuxturnaTM) in 2017 (USA) and Europe (2018). Post-marketing results confirm a significant therapeutic effect of this gene augmentation on rod function similar to that seen in the phase 1 to 3 clinical trials. The full-field chromatic light sensitivity test is an appropriate test to demonstrate early and sustained effects of treatment. Visual acuity and visual fields may improve in less advanced disease. Accelerated chorioretinal atrophy (CRA) is a previously unrecognised adverse effect that is now reported in 13 % to 50 % of treated eyes. If central, visual acuity loss and paracentral visual field defects may occur. Further studies are needed to identify patients at risk of CRA in order to maximize patient benefit from a costly intervention.

查看原文本刊更多论文

基因增强治疗与RPE65双等位基因突变相关的遗传性视网膜疾病患者的长期经验

RPE65双等位基因突变相关的遗传性视网膜变性（IRD）是目前唯一被批准进行基因治疗的IRD。本叙述性综述简要概述了该疾病，并更新了2017年（美国）和2018年（欧洲）批准使用voretigene neparvovec （LuxturnaTM）治疗后的最新文献。上市后的结果证实了这种基因增强对杆状细胞功能的显著治疗效果，类似于在1至3期临床试验中看到的效果。全视野色光敏感性试验是一种适当的试验，以证明早期和持续的治疗效果。在不太严重的疾病中，视力和视野可能会改善。加速的绒毛膜视网膜萎缩（CRA）是一种以前未被认识到的不良反应，现在在13%至50%的治疗眼睛中报道。如果是中枢性的，可能会出现视力下降和副中枢性视野缺损。需要进一步的研究来确定有CRA风险的患者，以便使患者从昂贵的干预中获益最大化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Medizinische Genetik GENETICS & HEREDITY-

自引率

9.10%

发文量

期刊介绍： medizinischegenetik is a scientific journal that is owned and published by the German Society of Human Genetics e.V. since 1989. The journal was founded by Prof. Jan Murken, München. Self-published until 2006, from 2007-2019 published at Springer Verlag and since 2020 at De Gruyter. medizinischegenetik serves education and training among colleagues, the interdisciplinary exchange of knowledge in all areas of human genetics in clinics, practice, research and teaching. Each issue of the quarterly journal deals with a focus that provides a comprehensive overview of current developments in specific clinical pictures, technical developments and therapeutic approaches. All reviews are written in English language. The journal thus creates a platform for the international exchange of knowledge and increased awareness of German research activities in the scientific community. In addition, medizinischegenetik contains information on activities in its own subject in the German-language section. This includes conference reports, association announcements, personnel matters, statements and guidelines. With health policy questions, historical retrospectives and comments on current developments, the profession takes a stand on human genetic issues in Germany, Austria and Switzerland.