Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701-9322, USA.
Neurotherapeutics. 2011 Oct;8(4):659-67. doi: 10.1007/s13311-011-0067-8.
Treating the central nervous system manifestations of subjects with neuropathic lysosomal storage diseases remains a major technical challenge. This is because of the low efficiency by which lysosomal enzymes in systemic circulation are able to traverse the blood brain barrier into the central nervous system. Intracranial transplantation of neural stems cells genetically modified to overexpress the respective deficient enzymes represents a potential approach to addressing this group of diseases. The unique properties of neural stem cells and progenitor cells, such as their ability to migrate to distal sites, differentiate into various cell types and integrate within the host brain without disrupting normal function, making them particularly attractive therapeutic agents. In addition, neural stem cells are amenable to ex vivo propagation and modification by gene transfer vectors. In this regard, transplanted cells can serve not only as a source of lysosomal enzymes but also as a means to potentially repair the injured brain by replenishing the organ with healthy cells and effecting the release of neuroprotective factors. This review discusses some of the well-characterized neural stem cell types and their possible use in treating neuropathic lysosomal storage diseases such as the Niemann Pick A disease.
治疗神经溶酶体贮积病患者的中枢神经系统表现仍然是一个主要的技术挑战。这是因为在全身循环中的溶酶体酶能够穿透血脑屏障进入中枢神经系统的效率很低。颅内移植经过基因修饰以过表达各自缺陷酶的神经干细胞代表了一种解决这组疾病的潜在方法。神经干细胞和祖细胞的独特特性，例如它们迁移到远端部位、分化为各种细胞类型并在不破坏正常功能的情况下整合到宿主大脑中的能力，使它们成为特别有吸引力的治疗剂。此外，神经干细胞可通过基因转移载体进行体外繁殖和修饰。在这方面，移植细胞不仅可以作为溶酶体酶的来源，还可以通过用健康细胞补充器官和释放神经保护因子来潜在地修复受损的大脑。本文讨论了一些特征明确的神经干细胞类型及其在治疗神经溶酶体贮积病（如尼曼-皮克 A 病）中的可能用途。
