腺相关病毒介导的基因治疗在儿童神经遗传罕见病中应用的现状与展望

Adeno-associated virus-mediated gene therapy for rare pediatric neurogenetic diseases:Current status and outlook

儿童神经遗传罕见病多起病早,缺乏特异性治疗手段,病死率高,严重危及患儿的健康及生命。以腺相关病毒(adeno-associated virus,AAV)介导的基因治疗为代表的疾病修正治疗为儿童神经遗传罕见病的治疗提供了新的方向。目前,AAV介导的基因治疗在儿童神经遗传罕见病治疗中有了突破性的进展,已有针对脊髓性肌萎缩症、芳香族L-氨基酸脱羧酶缺乏症、杜氏肌营养不良症的基因治疗药物获得美国食品药品管理局(Food and Drug Administration,FDA)/欧洲药品管理局(European Medicines Association,EMA)批准上市。多项临床前以及临床试验研究数据显示AAV介导的基因治疗在儿童神经遗传罕见病中有良好的应用前景,针对罕见病药物启动快速审批流程,这为神经遗传罕见病患儿的治疗带来了希望。但AAV介导的基因治疗属于新兴技术,存在着一定的风险和挑战,需要建立规范的监管体系以及健全的长期随访制度,以评估基因治疗的有效性及安全性。

Rare pediatric neurogenetic diseases always have early onset,no specific therapy,high mortality,and pose a severe risk to the health and survival of children.Adeno-associated virus(AAV)-mediated gene therapy,a type of disease-modifying therapy,provides a new option for the treatment of rare pediatric neurogenetic diseases and represents a significant advancement in the field.Currently,the US Food and Drug Administration(FDA)and the European Medicines Association(EMA)have approved AAV-mediated gene therapy medications for treating spinal muscular atrophy,aromatic L-amino acid decarboxylase deficiency,and Duchenne muscular dystrophy.Numerous preclinical and clinical trial research findings from recent years indicate that AAV-mediated gene therapy has a promising future in treating genetic disorders.The quick approval process for rare diseases medications may bring hope for the treatment of children with rare neurogenetic diseases.AAV-mediated gene therapy is an emerging technology with certain risks and challenges.It is necessary to establish a standardized regulatory system and a sound long-term follow-up system to evaluate the efficacy and safety of gene therapy.