EXTRACORPOREAL REMOVAL OF LDL WITH IMMOBILIZED ENZYMES

FAMILIAL HYPERCHOLESTEROLEMIA IS AN INHERITED DISORDER THAT RESULTS IN HIGH SERUM CHOLESTEROL LEVELS ATTRIBUTABLE TO AN ELEVATED LEVEL OF CHOLESTEROL-CARRYING LOW-DENSITY LIPO- PROTEIN (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. THIS PHASE IPROJECT WILL 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. 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, PROTOTYPE LDL-REMOVAL MODULES BOTH IN VITRO AND IN ANIMALS WILL BE CONSTRUCTED AND TESTED. THE PURPOSE OF THIS PROJECTIS THUS TO ESTABLISH THE TECHNICAL BASIS FOR ENZYMATIC LDL REMOVAL, TO CREATE A NEW BUSINESS OPPORTUNITY IN EXTRACOR- POREAL BLOOD PROCESSING, AND TO ADDRESS THE MEDICAL NEEDS OFAFFLICTED INDIVIDUALS WHO ARE POORLY SERVED BY EXISTING HYPERCHOLESTEROLEMIA THERAPIES.