GENE THERAPY FOR GAUCHER DISEASE AND OTHER INHERITED PROTEIN DEFICIENCIES

负责遗传的异常蛋白质的表征 影响神经系统的疾病允许正常的 cDNA和基因组DNA可用于纠正遗传蛋白 基因治疗的缺陷。 特别适合初 基因治疗的尝试是那些疾病（如戈谢病， 最常见的鞘脂病），其中全身和神经系统 这种疾病的表现是异常的结果， 骨髓来源的细胞，如巨噬细胞。 在这些情况下 将正常基因转移到特定组织或骨髓中 祖细胞或干细胞是一种基本的治疗方法。 使用 以溶酶体疾病戈谢病为模型， 逆转录病毒载体转移和表达人葡糖脑苷脂酶， 小鼠和Gaucher患者细胞系。 其他战略包括 研究包括受体介导的基因转移、移植 的神经祖细胞，以及使用新器官组成的， 重组改变的细胞作为蛋白质生产的仓库。 本研究的最初目标是基因治疗的应用 与非神经病表型相关 转基因动物模型 利用胚胎干细胞中的同源重组开发， 产生人类疾病的小鼠模型。 当我们理解 遗传性神经精神疾病的发病机制 疾病的改善，并作为逆转录病毒介导的基因表达， 特定的组织和细胞变得更可预测，我们可以扩展 基因疗法在治疗影响免疫系统的选定疾病中的应用 神经系统

The characterization of abnormal proteins responsible for genetic disorders affecting the nervous system permits the isolation of normal cDNA and genomic DNA that can be used to correct inherited protein deficiencies using gene therapy. Particularly suited for initial attempts at gene therapy are those disorders (such as Gaucher disease, the most common sphingolipidosis) in which the systemic and neurologic manifestations of the disorder are the consequence of abnormalities of bone marrow derived cells, like the macrophage. In these instances the transfer of normal genes to either specific tissue or bone marrow progenitor or stem cells is a rationale therapeutic approach. Using the lysosomal disorder Gaucher disease as a model, we utilize retroviral vectors to transfer and express human glucocerebrosidase in mouse and Gaucher patient cell lines. Other strategies being investigated include receptor mediated gene transfer, transplantation of neuroprogenitor cells, and the use of neo-organs consisting of recombinantly altered cells acting as depots of protein production. The initial goal of this research is the application of gene therapy to non-neuronopathic phenotypes. Transgenic animal models are developed using homologous recombination in embryonic stem cells to generate mouse models of human disease. When our understanding of the pathogenetic mechanisms of inherited neurologic and psychiatric diseases improves and as retroviral-mediated expression of genes in specific tissues and cells becomes more predictable, we can extend the use of gene therapy to treatment of selected disorders affecting the nervous system.