Wing Sum Chu, Joanne Ng, Simon N. Waddington, Manju A. Kurian
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引用次数: 0
摘要
先天性神经递质(NT)代谢异常是一组罕见的异质性疾病,主要表现为神经系统特征,如运动障碍、自主神经功能障碍和发育迟缓。该病与其他疾病的临床表现重叠,导致诊断和治疗的延误,而且有些疾病对口服药物治疗无效。针对小儿先天性代谢异常的基因疗法已被开发出来并应用于临床,迄今已有 38 项介入性临床试验正在进行中。此外,通过病毒基因疗法恢复多巴胺合成和神经传导的帕金森病疗法也已开发成功。最近,欧洲药品管理局(EMA)和药品与保健品监管局(MHRA)批准了一种针对 AADC 缺乏症的 AAV2 基因补充疗法,该疗法可在这类疾病中取得良好的疗效和安全性。在这篇综述中,我们介绍了治疗 NT 相关疾病的临床前和临床研究进展,并总结了 NT 基因治疗研究需要仔细考虑的潜在挑战。
Gene therapy for neurotransmitter-related disorders
Inborn errors of neurotransmitter (NT) metabolism are a group of rare, heterogenous diseases with predominant neurological features, such as movement disorders, autonomic dysfunction, and developmental delay. Clinical overlap with other disorders has led to delayed diagnosis and treatment, and some conditions are refractory to oral pharmacotherapies. Gene therapies have been developed and translated to clinics for paediatric inborn errors of metabolism, with 38 interventional clinical trials ongoing to date. Furthermore, efforts in restoring dopamine synthesis and neurotransmission through viral gene therapy have been developed for Parkinson's disease. Along with the recent European Medicines Agency (EMA) and Medicines and Healthcare Products Regulatory Agency (MHRA) approval of an AAV2 gene supplementation therapy for AADC deficiency, promising efficacy and safety profiles can be achieved in this group of diseases. In this review, we present preclinical and clinical advances to address NT-related diseases, and summarise potential challenges that require careful considerations for NT gene therapy studies.
期刊介绍:
The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).