GAUCHER'S DISEASE--BIOCHEMICAL AND CLINICAL STUDIES

高雪病的传统或新疗法依赖于广泛的 对该疾病的临床和基本科学知识。很多病人 已经进行了研究，并确定了重要的并发症。诊断 使用单抗的不同表型可以鉴定 神经系统症状前受累病例。代谢紊乱 对钙稳态的影响已被描述，维生素D的治疗方案 和钙补充剂正在评估中。的基础研究工作 葡萄糖脑苷酶已经产生了各种项目，以解决 作为酶一部分的生物化学、细胞生物学和分子遗传学 更深远的研究。 葡萄糖脑苷酶是这些溶酶体酶研究的模型 和蛋白质。这种协调一致的方法的结果揭示了 结构，生物合成，合成和降解速率，溶酶体 路由、凝集素结合和细胞对酶的摄取。更改 这些过程中的一些已经被描述为几个突变 基因导致了不同的疾病表型。此信息 提供了完善酶替代方法的数据。 结合这些进展的临床试验目前正在进行中。其他 项目导致了隔离、表达和转移 葡萄糖脑苷酶基因引发了基因转移的考虑 治疗高雪氏症。

Conventional or novel therapy for Gaucher's disease depends upon broad clinical and basic scientific knowledge of the disorder. Many patients have been studied and important complications identified. Diagnosis of different phenotypes using a monoclonal antibody permits identification of neurologically affected cases presymptomatically. A disorder metabolism affecting calcium homeostatis has been described and regimens of vitamin D and calcium supplementation are being evaluated. Basic research work on glucocerebrosidase has generated a variety of projects which address the biochemistry, cell biology, and molecular genetics of the enzyme as a part of more far-reaching studies. Glucocerebrosidase serves as a model for these studies of lysosomal enzymes and proteins. The results of this coordinated approach have revealed the structure, biosynthesis, rates of synthesis and degradation, lysosomal routing, lectin binding, and cellular uptake of the enzyme. Alterations of some of these processes have been described for several mutations of the gene resulting in different phenotypes of the disease. This information provides data from which the approach of enzyme replacement is perfected. A clinical trial incorporating these advances is currently underway. Other projects have resulted in the isolation, expression, and transfer of the gene for glucocerebrosidase leading to the consideration of gene transfer for Gaucher's disease.