EXTRACORPOREAL REMOVAL OF LDL WITH IMMOBILIZED ENZYMES

家族性高胆固醇血症是一种遗传性疾病， 血清胆固醇水平升高归因于 携带胆固醇的低密度脂蛋白（LDL）。 这种情况导致 LDL衍生的胆固醇在几种组织中的沉积，特别是 肌腱和动脉，导致心脏病发作的高发病率， 最终死亡。 现有的药物和血浆交换疗法 重大缺陷。 我们建议探索高胆固醇血症的治疗， 膜固定化酶系统，其去除携带胆固醇的 从血液中去除蛋白质，并将净化的血浆返回给患者。 血浆将与LDL降解酶接触，以使 能够从血浆中分离的LDL颗粒，例如，中 标准血液或膜过滤器。 在第一阶段，知识库将 建立，将允许合理设计的等离子体 用于体外去除低密度脂蛋白的分离器/生物反应器模块。 在 在第二阶段，我们将构建和测试原型LDL去除模块， 体外和动物体内。 因此，该项目的目的是为以下方面奠定技术基础： 酶促LDL去除，创造一个新的商业机会， 体外血液处理，并解决医疗需求， 受影响的人谁是现有的服务差 高胆固醇血症治疗。

Familial hypercholesterolemia is an inherited disorder that results in high serum cholesterol levels attributable to an elevated level of cholesterol-carrying low-density lipoprotein (LDL). This condition leads to deposition of LDL-derived cholesterol in several tissues, especially tendons and arteries, which results in a high incidence of heart attack and ultimately death. Existing drug and plasma exchange therapies have significant drawbacks. We propose to explore the treatment of hypercholesterolemia with a membrane-immobilized enzyme system that removes cholesterol-carrying protein from the blood and returns the cleansed plasma to the patient. Plasma will be contacted with an LDL-degrading enzyme in order to render the LDL particles capable of being separated from the plasma, e.g., in a standard blood or membrane filter. In Phase I, a knowledge base will be established that will permit the rational design of a plasma separator/bioreactor module for the extracorporeal removal of LDL. In Phase II, we will construct and test prototype LDL-removal modules both in vitro and in animals. The purpose of this project is thus to establish the technical basis for enzymatic LDL removal, to create a new business opportunity in extracorporeal blood processing, and to address the medical needs of afflicted individuals who are poorly served by existing hypercholesterolemia therapies.