肾上腺脑白质营养不良(ALD)是一种X连锁的过氧化物酶体疾病,发病率为14-17,000名男性中的1名。由ABCD1基因内的致病变异引起。到了成年,大约40%的病人发展为脑ALD,一个严重的,通常是进行性和致命的神经炎症性疾病,没有干预。
历史上,只有异基因造血干细胞移植(HSCT)已被证明可以阻止脑ALD的进展,在疾病过程早期进行HSCT时获得了更好的结果。最近,已经研究了一种基于慢病毒的基因治疗方法,作为同种异体移植的替代方法,用于治疗脑ALD。使用术语“造血干细胞移植”进行了重点文献综述,\'\'基因治疗\'和\'肾上腺脑白质营养不良\'包括相关文献,特别是比较基因治疗和HSCT结果的经验。我们回顾了HSCT在脑ALD中的历史和经验及其局限性,以及目前与脑ALD基因治疗试验相关的信息。
关于这种基于慢病毒的基因治疗方法及其相对风险和益处的数据仍在评估中。在使用同种异体HSCT进行脑ALD的经验的背景下,对这些信息进行了探索。
Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder with an incidence of 1 in 14-17,000 male births, caused by pathogenic variants within the ABCD1 gene. By adulthood, approximately 40% of the patients develop cerebral ALD, a severe, neuroinflammatory condition that is generally progressive and fatal without intervention.
Historically, only allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to halt progression of cerebral ALD, with superior outcomes obtained when HSCT is performed early in the disease process. More recently, a lentiviral-based gene therapy approach has been investigated as therapy for cerebral ALD as an alternative to allogeneic transplantation. A focused literature review was performed using the terms \'hematopoietic stem cell transplantation,\' \'gene therapy\' and \'adrenoleukodystrophy\' to include relevant literature, especially comparing the experience with gene therapy and HSCT outcomes. We review the history and experience with HSCT in cerebral ALD and its limitations, as well as the information currently available in association with the gene therapy trials for cerebral ALD.
The data regarding this lentiviral-based gene therapy approach and its relative risks and benefits is still being evaluated. This information is explored in the context of the experience with allogeneic HSCT for cerebral ALD.