文摘
摘要目的:的临床疗效评估单个intravitreal注入rAAV2/2 -ND4(GS010),一个临床实验的基因治疗ND4-LHON。
背景:LHON线粒体遗传疾病,导致严重的双边视神经疾病。线粒体的点突变ND4基因占所有LHON病例的75%。rAAV2/2 -ND4是一个基因疗法使allotopic表达式和交付的野生型ND4视网膜神经节细胞的线粒体蛋白质。
设计/方法:救援(NCT02652767)和反向(NCT02652780第三阶段,随机,双盲,假对照试验LHON G11778A -主题ND4突变收到一个单边intravitreal注入rAAV2/2 -ND4。视觉功能、视网膜解剖和生活质量监控了96周后管理。
并发的研究与一个等效注入3非人类的灵长类动物。
结果:在96年,周rAAV2/2 -ND4治疗眼睛的反向科目获得平均+ 15 ETDRS字母与基线相比。Sham-treated眼睛表现出相似的进步(+ 13 ETDRS字母),与预期的疾病的自然史。在救援,意味着BCVA恶化双眼的最低点,随后从48到每周96年并行改进。平均而言,rAAV2/2 -ND4治疗眼睛的救助对象获得+ 26个ETDRS字母相当于最低点BCVA相比。
一个临床相关的响应(CRR)从最低点在至少一个眼睛反向的78%和63%的救助对象。相比之下,自然历史的一份研究报告指出,只有28%的LHON受试者从最低点G11778A突变有自发的哭泣。
rAAV2/2——的存在ND4在非人类的灵长类动物的身体眼睛了。
结论:最终结果的救援和反向显示临床上有意义的改进的视觉功能。改善侧眼也可能被解释成rAAV2/2——的转移ND4sham-treated眼。
披露:大多数博士已经收到个人赔偿咨询、担任科学顾问委员会说,与Gensight或其他活动,赛诺菲安万特Genzyme。大多数博士接到GenSight研究支持。萨顿博士接到GenSight研究支持。从GenSight Klopstock所说已收到博士研究支持。Newman博士已经收到个人赔偿咨询、担任科学顾问委员会说,与GenSight或其他活动,Santhera,夸克。Newman博士已经收到GenSight和Santhera研究支持。Vignal-Clermont博士已经收到个人赔偿咨询、担任科学顾问委员会,与GenSight来说,或其他活动。Carelli博士接到GenSight研究支持。Yu-Wai-Man博士已经收到个人赔偿咨询、担任科学顾问委员会说,或其他活动GenSight生物制剂。Yu-Wai-Man博士接到GenSight研究支持。 Dr. Biousse has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Gensight Biologics.Dr. Sergott has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Mallinckrodt, EMDSerono, Biogen, Novartis, Sanofi-Genzyme, Merck, Clene Nanomedicine, GenSight, Nightstar, Alexion. Dr. Sergott has received research support from Mallinckrodt, Biogen, Novartis.Dr. Katz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Gensight Biologics, Employee. Dr. DeBusk holds stock and/or stock options in DeRoyal. Dr. Blouin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GenSight Biologics. Dr. Chevalier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GenSight Biologics. Dr. Burguiere has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GenSight Biologics. Dr. Taiel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GenSight Biologics. 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.
