Division of Gene Therapy, Research Center for Medical Sciences/Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
J Hum Genet. 2019 Feb;64(2):139-143. doi: 10.1038/s10038-018-0537-5. Epub 2018 Nov 29.
Gene therapies for lysosomal storage diseases (LSD) and peroxisomal diseases (PD) are rapidly advancing. Most LSDs and PDs are characterized by brain involvement, prompting the development of therapies targeting the brain. There are two types of gene therapy for brain involvement in LSD and PD, i.e., the direct transfer of a therapeutic gene into brain cells and hematopoietic stem cell-targeted gene therapy. The rationale for the latter approach is that brain microglia are derived from hematopoietic cells. Thus, gene-corrected hematopoietic cells migrate into the brain and differentiate into microglial cells. These gene-corrected microglial cells correct the metabolic defects associated with LSD and reduce inflammation in PD and LSD, leading to a clinical benefit. Gene editing technology has recently been applied in this area and a trial focused on LSD is currently ongoing. Although these approaches are still under investigation, very encouraging results have been obtained. This review provides an overview of recently developed gene therapies for various LSDs and PDs, including the results of clinical trials, with an emphasis on the benefits of this approach for these diseases.
溶酶体贮积症（LSD）和过氧化物酶体疾病（PD）的基因治疗正在迅速发展。大多数 LSD 和 PD 都有脑受累的特征，这促使人们开发针对大脑的治疗方法。针对 LSD 和 PD 的脑受累有两种类型的基因治疗，即直接将治疗基因转入脑细胞和针对造血干细胞的基因治疗。后一种方法的原理是脑小胶质细胞来源于造血细胞。因此，经过基因修正的造血细胞迁移到大脑中并分化为小胶质细胞。这些经过基因修正的小胶质细胞纠正与 LSD 相关的代谢缺陷，并减少 PD 和 LSD 中的炎症，从而带来临床获益。基因编辑技术最近已应用于该领域，目前正在进行一项专注于 LSD 的试验。尽管这些方法仍在研究中，但已经取得了非常令人鼓舞的结果。本综述概述了最近开发的各种 LSD 和 PD 的基因治疗方法，包括临床试验结果，并重点介绍了这种方法对这些疾病的益处。
