血液造血干细胞基因疗法在X链 adrenoleukodystrophy的一个lentiviral载体
Nathalie Cartier1, Salima Hacein-Bey-Abina, Cynthia C Bartholomae
1INSERM UMR745, University Paris-Descartes, 75279 Paris, France.
Science (New York, N.Y.)
|November 7, 2009
概括
使用lentiviral载体的基因治疗成功地通过纠正造血干细胞,在X链 adrenoleukodystrophy (ALD) 患者中通过纠正造血干细胞,成功地阻止了大脑脱髓化,提供了一个新的治疗选择.
科学领域:
- 神经学 神经学
- 遗传学 是一个遗传学.
- 血液学 血液学 血液学
背景情况:
- 与X相关的 adrenoleukodystrophy (ALD) 是一种严重的儿科失髓性脑疾病.
- ALD是由ALD蛋白缺陷引起的,ALD蛋白由ABCD1基因编码.
- 全基性造血细胞移植 (HCT) 可以阻止ALD的进展,但需要匹配的捐赠者.
研究的目的:
- 评估在缺乏匹配捐赠者的患者中治疗ALD的lentiviral介导基因疗法的疗效.
- 评估自主造血干细胞的ex vivo基因校正潜力.
主要方法:
- 自主CD34+细胞从两个ALD患者中收集.
- 细胞通过使用编码野生类型ABCD1.1.的隐形病毒载体进行了ex vivo基因校正.
- 经过骨髓缩条件后,纠正后的细胞被重新注入.
主要成果:
- 观察到多克隆细胞的复合,其中9-14%的白细胞表达了ALD蛋白.
- 血液造血干细胞在患者中成功转化.
- 输注后14-16个月,大脑脱髓化停止了,与异构HCT结果相比.
结论:
- 造血干细胞的lentiviral介导基因疗法是ALD的可行的治疗方法.
- 这种方法为ALD患者提供了临床益处,特别是那些没有匹配捐赠者的患者.
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