在干细胞基因治疗后,在MPSII的小鼠模型中持续的长期疾病纠正
Stuart Ellison1, Aiyin Liao1, Hélène F E Gleitz1
1Stem Cell & Neurotherapies Group, University of Manchester, Manchester M13 9PT, UK.
Molecular therapy. Methods & clinical development
|November 3, 2023
概括
使用IDS的血造干细胞基因疗法.ApoEII在小鼠中提供了对II型多糖瘤 (MPSII) 的持续纠正. 这种针对大脑的方法有效清除存储物质并防止神经退行,显示了长期的安全性和有效性.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 生物化学 生物化学
背景情况:
- 粘多糖症II型 (MPSII) 是一种遗传性溶酶体储存疾病,影响多个器官并导致神经退行.
- 目前的酶替代疗法无法穿越血脑屏障,限制了它对与大脑相关的MPSII症状的有效性.
- 造血干细胞基因疗法为向大脑输送治疗酶提供了一个潜在的解决方案.
研究的目的:
- 在小鼠模型中评估针对MPSII的大脑基因治疗的长期疗效和安全性.
- 为了评估持续的酶活性,储存物质清除和治疗后的神经病理纠正.
- 确定IDS.ApoEII基因治疗对系统性和中枢神经系统疾病表现的潜力.
主要方法:
- 通过血液造血干细胞基因疗法对MPSII小鼠进行与ApoEII (IDS.ApoEII) 融合的lentiviral IDS的治疗.
- 与表达本地IDS的lentivirus和未经操纵的骨髓移植进行比较.
- 长期评估 (12-16个月) 酶活性,糖氨基甘油储存,神经炎症标志物 (星病,微病),细胞因子/化学因子水平,视网膜健康.
主要成果:
- 在IDS.ApoEII治疗小鼠的器官中观察到持续的IDS酶活性,治疗后长达16个月.
- 在大脑和外周器官中,存储物质的持续清除.
- 维持了神经炎症的纠正,改变了细胞因子/化学因子,并显著减少了视网膜缩.
结论:
- 用IDS针对大脑的造血干细胞基因疗法.ApoEII在预防小鼠MPSII系统和神经表型方面表现出持续的有效性.
- 该疗法显示长期安全性,没有观察到毒性.
- 这些发现支持IDS.ApoEII基因治疗在MPSII患者的临床应用的潜力,包括那些有严重神经疾病的患者.
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