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 to 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 membrane filter. In Phase I, a knowledge base has been established that supports the technical feasibility of a plasma separator/bioreactor module for the extracorporeal removal of LDL. In Phase II, we will extend that knowledge base and construct and test prototype LDL-removal modules both in vitro and in animals. The purpose of this project is thus to demonstrate a novel and beneficial approach to 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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44HL034909-03
Application #
2217685
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1988-09-30
Project End
1991-06-30
Budget Start
1989-09-30
Budget End
1991-06-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Sepracor, Inc.
Department
Type
DUNS #
City
Marlborough
State
MA
Country
United States
Zip Code
01752