Center for Advanced Retinal and Ocular Therapeutics (CAROT), Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; The Children's Hospital of Philadelphia (CHOP), Philadelphia, PA, USA.
Center for Advanced Retinal and Ocular Therapeutics (CAROT), Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Mol Ther. 2021 Feb 3;29(2):442-463. doi: 10.1016/j.ymthe.2020.11.029. Epub 2020 Dec 3.
Until recently, there was no approved treatment for a retinal degenerative disease. Subretinal injection of a recombinant adeno-associated virus (AAV) delivering the normal copy of the human RPE65 cDNA led to reversal of blindness first in animal models and then in humans. This led to the first US Food and Drug Administration (FDA)-approved gene therapy product for a genetic disease, voretigene neparvovec-rzyl (Luxturna). Luxturna was then approved by the European Medicines Association and is now available in the US through Spark Therapeutics and worldwide through Novartis. Not only has treatment with Luxturna changed the lives of people previously destined to live a life of blindness, but it has fueled interest in developing additional gene therapy reagents targeting numerous other genetic forms of inherited retinal disease. This review describes many of the considerations for administration of Luxturna and describes how lessons from experience with Luxturna could lead to additional gene-based treatments of blindness.
直到最近,还没有批准治疗视网膜退行性疾病的方法。视网膜下注射携带正常人类 RPE65 cDNA 的重组腺相关病毒(AAV)首先在动物模型中,然后在人类中导致失明逆转。这导致了第一个获得美国食品和药物管理局(FDA)批准的用于治疗遗传疾病的基因治疗产品,voretigene neparvovec-rzyl(Luxturna)。Luxturna 随后获得了欧洲药品管理局的批准,现在可以通过 Spark Therapeutics 在全美范围内获得,在全球范围内可以通过诺华公司获得。Luxturna 的治疗不仅改变了以前注定失明的人的生活,而且激发了人们开发针对许多其他遗传性视网膜疾病的基因治疗试剂的兴趣。这篇综述描述了 Luxturna 给药的许多注意事项,并描述了从 Luxturna 经验中获得的经验教训如何为治疗失明的其他基因治疗方法提供指导。