Paving a way to treat spastic paraplegia 50.
Paving a way to treat spastic paraplegia 50.
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DOI：
10.1172/jci170226
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发表时间：
2023-05-15
期刊：
影响因子：
--
通讯作者：
Deng HX
中科院分区：
文献类型：
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作者：
Brent JR;Deng HX
痉挛截瘫50(SPG50)是一种罕见的神经退行性疾病，由AP4M1功能缺失突变引起。对于SPG50或任何其他类型的SPG，目前还没有有效的治疗方法，目前的治疗仅限于对症治疗。在这一期的JCI中，Chen等人。提供来自临床前研究的有希望的数据，这些研究评估了AAV介导的AP4M1基因替代疗法对SPG50的有效性和安全性。AAV/AP4M1基因替换部分挽救了SPG50细胞和小鼠模型的功能缺陷，在啮齿动物和猴子中具有可接受的安全性。这项工作代表着SPG50疗法的治疗开发方面的实质性进展，为将AAV9/AP4M1基因疗法用于临床试验建立了标准。
Spastic paraplegia 50 (SPG50) is a rare neurodegenerative disease caused by loss-of-function mutations in AP4M1. There are no effective treatments for SPG50 or any other type of SPG, and current treatments are limited to symptomatic management. In this issue of the JCI, Chen et al. provide promising data from preclinical studies that evaluated the efficacy and safety profiles of an AAV-mediated AP4M1 gene replacement therapy for SPG50. AAV/AP4M1 gene replacement partly rescued functional defects in SPG50 cellular and mouse models, with acceptable safety profiles in rodents and monkeys. This work represents a substantial advancement in therapeutic development of SPG50 treatments, establishing the criteria for taking AAV9/AP4M1 gene therapy to clinical trials.