EXTRACORPOREAL REMOVAL OF LDL WITH IMMOBILIZED ENZYMES

用固定化酶体外去除 LDL

• 批准号: 3500672
• 负责人: STEPHEN L MATSON
• 金额: $ 5万
• 依托单位: SEPRACOR, INC.
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-15 至 1986-10-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3500672
• 关键词: bioreactors; blood filtration; cholesterol; clinical biomedical equipment; familial hyperlipoproteinemia type II; hemodialysis; hollow fiber separation technique; immobilized enzymes; low density lipoprotein; phospholipase C

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.

家族性高胆固醇血症是一种遗传性疾病，可导致高胆固醇血症