STUDIES OF GAUCHER DISEASE AND OTHER NEUROGENETIC DISORDERS TOWARD GENE THERAPY

人类遗传性神经系统疾病的临床研究 对于诊断技术的成功发展至关重要， 治疗策略。 这一目标还得到了一个全面的 疾病的生物化学和临床异质性的知识。 戈谢病是最常见的鞘脂病， 一个模型，因为发生神经病和非神经病， 神经病理表型 广谱临床的基础 还可以研究主要类型的疾病的多样性。 一旦 这种酶系统参与的病理生理机制 缺乏症的理解和治疗，神经的治疗 系统功能障碍可能会更合理地处理。 基础研究 葡萄糖脑苷脂酶是戈谢病中缺乏的酶， 更详细地了解其结构、生物合成、细胞内 路由和酶的周转。 这些研究补充了其他 我们分支的研究重点是调查潜在的 和基因转移作为治疗方法的有效性。 针对性 胚胎干细胞中的同源重组用于开发 适当的戈谢病和其他遗传疾病的转基因动物模型 影响神经系统的疾病。 重组生产人 酶和激活蛋白是针对发展的影响， 酶替代和基因治疗。

The clinical study of human genetic disorders affecting the nervous system is important for the successful development of diagnostic techniques and strategies for therapy. This goal is also facilitated by a comprehensive knowledge of the biochemistry and clinical heterogeneity of the disorder. Gaucher disease, the most common sphingolipidosis, is extremely useful as a model because of the occurrence of both neuronopathic and non- neuronopathic phenotypes. The basis of the broad spectrum of clinical diversity within the major types of the disorder can also be studied. Once the pathophysiologic mechanisms of systematic involvement in this enzyme deficiency disorder are understood and treatable, the therapy of nervous system dysfunction may be more rationally approached. Basic research on glucocerebrosidase, the enzyme deficient in Gaucher disease, has generated a more detailed understanding of the structure, biosynthesis, intracellular routing, and turnover of the enzyme. These studies complement other studies within our branch focusing on the investigation of the potential and efficacy of gene transfer as a therapeutic approach. Targeted homologous recombination in embryonic stem cells is used to develop appropriate transgenic animal models of Gaucher disease and other genetic disorders affecting the nervous system. Recombinant production of human enzymes and activator proteins is directed toward the development of effect enzyme replacement and gene therapy.