Hematopoietic Stem Cell Transplantation and Hematopoietic Stem Cell Gene Therapy in X-Linked Adrenoleukodystrophy
Hematopoietic Stem Cell Transplantation and Hematopoietic Stem Cell Gene Therapy in X-Linked Adrenoleukodystrophy
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DOI：
10.1111/j.1750-3639.2010.00394.x
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发表时间：
2010-07-01
期刊：
影响因子：
6.4
通讯作者：
Aubourg, Patrick
中科院分区：
文献类型：
--
作者：
Cartier, Nathalie;Aubourg, Patrick
异基因造血干细胞移植（HSCT）是唯一的治疗方法，可以阻止大脑脱髓鞘的X-连锁肾上腺脑白质营养不良（ALD）的男孩，并导致长期在一个良好的生活质量，提供该程序是在疾病的早期阶段进行。同种异体HSCT的类似益处已在患有脑ALD的成人中得到证实。然而，目前尚不清楚同种异体造血干细胞移植是否可以预防或挽救肾上腺脊髓神经病。同种异体造血干细胞移植仍然与显着的发病率和死亡率的风险，特别是在成人，并不是所有的ALD患者有捐助者，尽管脐带血的可用性。缺乏可以预测脑疾病进展的生物学标志物是在适当的时候提出ALD患者异基因HSCT的主要限制。最近，使用慢病毒载体的HSC基因治疗在两名没有人类白细胞抗原（HLA）匹配供体的脑ALD男孩中显示出与同种异体HSCT相当的疗效。如果这些结果在一系列患者中得到证实，HSC基因治疗可能成为所有发生脑脱髓鞘的ALD男性患者的第一治疗选择。
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only therapeutic approach that can arrest cerebral demyelination of X-linked adrenoleukodystrophy (ALD) in boys and results in long-term in a good quality of life, provided the procedure is performed at an early stage of disease. Similar benefits of allogeneic HSCT have been demonstrated in adults with cerebral ALD. However, it is not yet known whether allogeneic HSCT can prevent or rescue adrenomyeloneuropathy. Allogeneic HSCT remains associated with significant morbidity and mortality risks, particularly in adults, and not all ALD patients have donors despite the availability of cord blood. The absence of biological markers that can predict the evolutivity of cerebral disease is a major limitation to propose in due time allogeneic HSCT to ALD patients. Recently, HSC gene therapy using lentiviral vector was shown to have comparable efficacy than allogeneic HSCT in two boys with cerebral ALD who had no Human-leukocyte-antigen (HLA)-matched donor. If these results are confirmed in an extended series of patients, HSC gene therapy may become the first therapeutic option for all ALD male patients who develop cerebral demyelination.