Retina Foundation of the Southwest, Dallas, TX, USA.
Foundation Fighting Blindness, Columbia, MD, USA.
Transl Vis Sci Technol. 2023 Jun 1;12(6):5. doi: 10.1167/tvst.12.6.5.
X-linked retinitis pigmentosa (XLRP) is a rare inherited retinal disease manifesting as impaired night vision and peripheral vision loss that progresses to legal blindness. Although several trials of ocular gene therapy for XLRP have been conducted or are in progress, there is currently no approved treatment. In July 2022, the Foundation Fighting Blindness convened an expert panel to examine relevant research and make recommendations for overcoming the challenges and capitalizing on the opportunities in conducting clinical trials of RPGR-targeted therapy for XLRP. Data presented concerned RPGR structure and mutation types known to cause XLRP, RPGR mutation-associated retinal phenotype diversity, patterns in genotype/phenotype relationships, disease onset and progression from natural history studies, and the various functional and structural tests used to monitor disease progression. Panel recommendations include considerations, such as genetic screening and other factors that can impact clinical trial inclusion criteria, the influence of age on defining and stratifying participant cohorts, the importance of conducting natural history studies early in clinical development programs, and the merits and drawbacks of available tests for measuring treatment outcomes. We recognize the need to work with regulators to adopt clinically meaningful end points that would best determine the efficacy of a trial. Given the promise of RPGR-targeted gene therapy for XLRP and the difficulties encountered in phase III clinical trials to date, we hope these recommendations will help speed progress to finding a cure.
Examination of relevant data and recommendations for the successful clinical development of gene therapies for RPGR-associated XLRP.
X 连锁性视网膜色素变性（XLRP）是一种罕见的遗传性视网膜疾病，表现为夜间视力和周边视力下降，进而导致法定失明。尽管已经进行或正在进行几项针对 XLRP 的眼部基因治疗试验，但目前尚无批准的治疗方法。2022 年 7 月，盲症基金会召集了一个专家小组，检查相关研究并就克服临床试验的挑战和利用 RPGR 靶向治疗 XLRP 的机会提出建议。提交的数据涉及已知导致 XLRP 的 RPGR 结构和突变类型、RPGR 突变相关的视网膜表型多样性、基因型/表型关系的模式、自然史研究中的疾病发作和进展，以及用于监测疾病进展的各种功能和结构测试。小组建议包括考虑因素，如遗传筛选和其他可能影响临床试验纳入标准的因素、年龄对定义和分层参与者队列的影响、在临床开发计划早期进行自然史研究的重要性，以及现有测试用于衡量治疗效果的优缺点。我们认识到需要与监管机构合作，采用最能确定试验疗效的临床有意义的终点。鉴于 RPGR 靶向基因治疗对 XLRP 的前景以及迄今为止在 III 期临床试验中遇到的困难，我们希望这些建议将有助于加快寻找治疗方法的进展。
X 连锁性视网膜色素变性（XLRP）是一种罕见的遗传性视网膜疾病，表现为夜间视力和周边视力下降，进而导致法定失明。尽管已经进行或正在进行几项针对 XLRP 的眼部基因治疗试验，但目前尚无批准的治疗方法。2022 年 7 月，盲症基金会召集了一个专家小组，检查相关研究并就克服临床试验的挑战和利用 RPGR 靶向治疗 XLRP 的机会提出建议。提交的数据涉及已知导致 XLRP 的 RPGR 结构和突变类型、RPGR 突变相关的视网膜表型多样性、基因型/表型关系的模式、自然史研究中的疾病发作和进展，以及用于监测疾病进展的各种功能和结构测试。小组建议包括考虑因素，如遗传筛选和其他可能影响临床试验纳入标准的因素、年龄对定义和分层参与者队列的影响、在临床开发计划早期进行自然史研究的重要性，以及现有测试用于衡量治疗效果的优缺点。我们认识到需要与监管机构合作，采用最能确定试验疗效的临床有意义的终点。鉴于 RPGR 靶向基因治疗对 XLRP 的前景以及迄今为止在 III 期临床试验中遇到的困难，我们希望这些建议将有助于加快寻找治疗方法的进展。
翻译后的文本是对原文的准确表达，没有添加任何个人观点或解释。
