RT期刊文章SR电子T1 rAAV2/2-ND4治疗LHON: 72周的数据反向三期临床试验(Plen02.002)摩根富林明神经病学神经学乔FD Lippincott Williams &威尔金斯SP Plen02.002 VO 92 15 A1 Mark l .大多数A1阿尔弗雷多·萨顿首页补充A1托马斯Klopstock A1凯瑟琳Vignal-Clermont A1南希·j·纽曼A1 Valerio Carelli A1帕特里克Yu-Wai-Man A1 Jose-Alain萨赫勒A1巴雷特Katz年2019 UL //www.ez-admanager.com/content/92/15_Supplement/Plen02.002.abstract AB目的:评估的功效单一intravitreal注入rAAV2/2-ND4 (GS010),开展基因治疗由于ND4-LHON视力丧失。背景:LHON线粒体遗传疾病,导致两国的中心视力丧失。在线粒体ND4点突变基因占所有LHON病例的75%。rAAV2/2-ND4是基因疗法使allotopic野生型ND4蛋白质的表达和交付视网膜神经节细胞的线粒体。设计/方法:反向(NCT02652780)是第三阶段,随机、多中心、双盲、假对照试验的37 LHON科目G11778A-ND4突变。所有收到一个单边intravitreal rAAV2/2-ND4注入。视觉功能和测量相关视网膜解剖监控了72周后治疗。结果:一周72 + 15的改进ETDRS字母是rAAV2/2-ND4治疗眼睛。Sham-treated眼睛还显示改善灵敏度(+ 12 ETDRS字母)。对比敏感度也改善了:GS010-treated sham-treated眼睛分别获得了平均0.15 + 0.21 LogCS + LogCS,与基线相比。GS010-treated眼睛的比例达到了临床有意义的改善至少0.3 LogCS(45.9%)在统计学上显著高于sham-treated眼睛(24.9%;p = 0.0047)。 Ganglion cell layer (GCL) volume, papillo-macular bundle thickness and total macular ETDRS thickness were significantly preserved in treated vs. sham eyes; all 3 differences reaching statistical significance.Conclusions: Seventy-two weeks after rAAV2/2-ND4 administration, a clinically meaningful improvement in visual functions and sustained preservation of LHON-relevant retinal anatomy were seen in drug-treated eyes, suggesting that the biological targets of this gene therapy were successfully engaged.Disclosure: Dr. Moster has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Gensight and Sanofi Genzyme. Dr. Moster has received research support from GenSight. Dr. Sadun has received research support from GenSight. Dr. Klopstock has received research support from GenSight. Dr. Vignal-Clermont has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GenSight. Dr. Newman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GenSight Biologics and Quark Pharmaceuticals. Dr. Newman has received research support from GenSight Biologics and Santhera Pharmaceuticals. Dr. Carelli has received research support from GenSight. Dr. Yu-Wai-Man has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GenSight Biologics. Dr. Yu-Wai-Man has received research support from GenSight. Dr. Sahel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GenSight, Pixium, Tilak, Prophesee, Chronolife, Sparing Vision, Spark, Stargazer, Sanofi. Dr. Sahel has received research support from GenSight. Dr. Katz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Gensight Biologics.