ENZYME IMMOBILIZATION FOR REMOVAL OF TOXIC METABOLITES

ENZYME DEFICIENCIES ASSOCIATED WITH INBORN METABOLIC DEFECTSARE USUALLY FATAL WITHIN THE FIRST FEW YEARS OF LIFE. TREATMENTS SUCH AS DIET MANIPULATION, GENE REPLACEMENT THERAPY, CHEMOTHERAPY, TRANSFUSIONS, TRANSPLANTATIONS, AND PERITONEAL DIALYSIS HAVE PRODUCED MARGINAL IMPROVEMENTS IN THESE PATIENTS. ENZYME REPLACEMENT THERAPY IS AN APPEALING ALTERNATIVE OR ADJUNCT TO THESE TREATMENTS. HOWEVER, DIRECT ENZYME REPLACEMENT HAS LED TO HYPERSENSITIVITY RESPONSES IN THE HOSTS, AND INSTABILITY OF SUCH PREPARATIONSHAS MADE USE OF SUCH PROCEDURES IMPRACTICAL. WE PROPOSE TO EXPLORE IMMOBILIZATION CHEMISTRIES FOR DEVELOPMENT OF ENZYME-ACTIVATED SURFACES FOR EXTRACORPOREAL REMOVAL OF TOXIC METABOLITIES. WE WILL USE PHOTOCHEMICAL PROCEDURES TOACTIVATE SUPPORT MATRICES FOR SUBSEQUENT COUPLING TO THE MODEL ENZYME, ARGINASE. SUCCESSFUL DEMONSTRATION OF THE IMPROVED ENZYME ACTIVITIES AFFORDED BY THIS TECHNOLOGY IN ANIN VITRO BLOOD SYSTEM WILL LEAD TO CONTINUATION OF THIS PROJECT WITH A CONSULTANT LABORATORY FOR PHASE II ANIMAL MODEL STUDIES.