University Eye Hospital, Centre for Ophthalmology, Tübingen, Germany.
Institute for Ophthalmic Research, Centre for Ophthalmology, Tübingen, Germany.
Retina. 2020 Jan;40(1):160-168. doi: 10.1097/IAE.0000000000002360.
Choroideremia (CHM) is a rare inherited retinal degeneration resulting from mutation of the CHM gene, which results in absence of functional Rab escort protein 1 (REP1). We evaluated retinal gene therapy with an adeno-associated virus vector that used to deliver a functional version of the CHM gene (AAV2-REP1).
THOR (NCT02671539) is a Phase 2, open-label, single-center, randomized study. Six male patients (51-60 years) with CHM received AAV2-REP1, by a single 0.1-mL subretinal injection of 10 genome particles during vitrectomy. Twelve-month data are reported.
In study eyes, 4 patients experienced minor changes in best-corrected visual acuity (-4 to +1 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); one gained 17 letters and another lost 14 letters. Control eyes had changes of -2 to +4 letters. In 5/6 patients, improvements in mean (95% confidence intervals) retinal sensitivity (2.3 [4.0] dB), peak retinal sensitivity (2.8 [3.5] dB), and gaze fixation area (-36.1 [66.9] deg) were recorded. Changes in anatomical endpoints were similar between study and control eyes. Adverse events were consistent with the surgical procedure.
Gene therapy with AAV2-REP1 can maintain, and in some cases, improve, visual acuity in CHM. Longer term follow-up is required to establish whether these benefits are maintained.
脉络膜视网膜变性（CHM）是一种罕见的遗传性视网膜退行性疾病，由 CHM 基因突变引起，导致功能性 Rab 衔接蛋白 1（REP1）缺失。我们评估了使用腺相关病毒载体进行的视网膜基因治疗，该载体用于递送功能性 CHM 基因（AAV2-REP1）。
THOR（NCT02671539）是一项 2 期、开放标签、单中心、随机研究。6 名男性 CHM 患者（51-60 岁）在玻璃体切除术中接受了单次 0.1 毫升视网膜下注射 10 个基因组的 AAV2-REP1。报告了 12 个月的数据。
在研究眼中，4 名患者最佳矫正视力出现轻微变化（-4 至+1 早期糖尿病视网膜病变研究[ETDRS]字母）；1 人增加了 17 个字母，另 1 人减少了 14 个字母。对照眼的变化为-2 至+4 个字母。在 5/6 名患者中，平均（95%置信区间）视网膜敏感度（2.3[4.0]dB）、峰值视网膜敏感度（2.8[3.5]dB）和注视固定区域（-36.1[66.9]deg）有所改善。研究眼和对照眼的解剖终点变化相似。不良事件与手术过程一致。
AAV2-REP1 基因治疗可维持 CHM 患者的视力，并在某些情况下提高视力。需要进行更长时间的随访，以确定这些益处是否得以维持。
