ENZYME REPLACEMENT THERAPY IN DISORDERS THAT AFFECT THE CENTRAL NERVOUS SYSTEM

影响中枢神经系统疾病的酶替代疗法

• 批准号: 6163060
• 负责人: R O BRADY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6163060
• 关键词: Gaucher's disease; beta galactosidase; central nervous system; drug delivery systems; drug metabolism; drug receptors; enzyme therapy; gangliosides; gangliosidosis GM1; glucosylceramidase; inborn metabolism disorder; injection /infusion; metabolism disorder chemotherapy; neuronal transport; neurons; nonhuman therapy evaluation; tissue /cell culture

Because enzyme replacement therapy is so effective for patients with Type 1 (non-neuronpathic) Gaucher's disease, we have performed investigations to try to deliver the required glucocerebrosidase to neurons in the central nervous system in order to treat patients with the neuronpathic forms of this disorder. We found that mannose-terminal glucocerebrosidase is stable within the substance of the brain following convection-enhanced intracerebral injection. Moreover, the enzyme migrates from the site of injection toward the cortex where neurons containing stored glucocerebroside occur. We have discovered that mannose-terminal glucocerebrosidase is taken up by cultured LAN-2 and other differentiated neurons in tissue culture, but this uptake is different from that mediated by the mannose lectin on the plasma cell membrane of macrophages. We shall determine the nature of the receptor on neurons and attempt to exploit it to deliver glucocerebrosidase and other supplemental enzymes to treat various neurometabolic disorders.

因为酶替代疗法对慢性阻塞性肺疾病患者非常有效 1型(非神经性)高雪氏病，我们进行了 试图将所需的葡萄糖脑苷酶传递给 中枢神经系统中的神经元，以便治疗患者 这种疾病的神经性表现形式。我们找到了甘露糖终端 葡萄糖脑苷酶在下列脑组织物质中是稳定的 对流增强脑内注射。此外，这种酶 从注射部位向皮层迁移，在那里神经元 含有储存的葡萄糖脑苷出现。我们发现， 甘露糖端葡萄糖脑苷酶被培养的LAN-2和 组织培养中的其他分化神经元，但这种摄取是 不同于浆细胞上甘露糖凝集素的介导 巨噬细胞膜。我们将确定受体的性质 并试图利用它来传递葡萄糖脑苷酶和 用于治疗各种神经代谢紊乱的其他补充酶。