PDF(Pubmed)
Abstract：
Gene therapies have potential to improve outcomes of severe diseases after only a single administration. Novel therapies are continually being developed using knowledge gained from prior successes, a concept known as scientific spillover. Gene therapy advancement requires extensive development at each stage: preclinical work to create and evaluate vehicles for delivery of the therapy, design of clinical development programs, and establishment of a large-scale manufacturing process. Pioneering gene therapies are generating spillover as investigators confront myriad issues specific to this treatment modality. These include frameworks for construct engineering, dose evaluation, patient selection, outcome assessment, and safety monitoring. Consequently, the benefits of these therapies extend beyond offering knowledge for treating any one disease to establishing new platforms and paradigms that will accelerate advancement of future gene therapies. This impact is even more profound in rare diseases, where developing therapies in isolation may not be possible. This review describes some instances of scientific spillover in healthcare, and specifically gene therapy, using delandistrogene moxeparvovec (SRP-9001), a gene therapy recently approved by the US Food and Drug Administration for the treatment of ambulatory pediatric patients aged 4-5 years with Duchenne muscular dystrophy with a confirmed mutation in the DMD gene, as a case study.
摘要：
基因疗法仅在单次给药后就有可能改善严重疾病的预后。使用从先前的成功中获得的知识不断开发新的疗法，一个被称为科学溢出的概念。基因治疗的进步需要在每个阶段进行广泛的发展：临床前工作，以创建和评估治疗的载体，临床开发计划的设计，并建立大规模的制造工艺。随着研究人员面对这种治疗方式特有的无数问题，开创性的基因疗法正在产生溢出效应。这些包括建筑工程的框架，剂量评估，患者选择,结果评估，和安全监测。因此,这些疗法的好处不仅限于提供治疗任何一种疾病的知识，还可以建立新的平台和范例，以加速未来基因疗法的发展。这种影响在罕见疾病中更为深远，单独开发疗法可能是不可能的。这篇综述描述了医疗保健领域科学溢出的一些实例，特别是基因治疗，使用delandistrogenemoxeparvovec（SRP-9001），美国食品和药物管理局最近批准的一种基因疗法，用于治疗4-5岁患有Duchenne肌营养不良症的非卧床儿科患者，作为一个案例研究。
