DEVELOPMENT OF GROWTH HORMONE RELEASING FACTOR AGONISTS

HUMAN GROWTH HORMONE (HGH) IS A MAJOR REGULATOR OF GROWTH AND METABOLISM. RECOMBINANT HGH HAS BEEN USED TO CORRECT PITUITARY DWARFISM. RECENTLY, RECOMBINANT HGH HAS BEEN SHOWN TO COUNTERACT VARIOUS DEGENERATIVE PROCESSES ASSOCIATED WITH AGING. OTHER POTENTIAL USES INCLUDE TREATMENT OF OBESITY AND ACUTE CATABOLIC ILLNESSES. LONG-TERM THERAPY WITH RECOMBINANT HGH PROTEIN, HOWEVER, IS EXPENSIVE (UP TO $ 30,000 PER PATIENT/YEAR). HGH HAS TO BE ADMINISTERED BY INJECTION. HUMAN GROWTH HORMONE RELEASING FACTOR (HGRF) ACTS AT THE LEVEL OF GENE TRANSCRIPTION TO STIMULATE ENDOGENOUS HGH PRODUCTION. THE GOAL OF THIS PROJECT IS TO IDENTIFY LOW-COST HGRF AGONISTS, WHICH CAN BE ORALLY ADMINISTERED AND SPECIFICALLY INCREASE ENDOGENOUS HGH PRODUCTION BY TRANSCRIPTIONAL STIMULATION OF THE HGH PROMOTER. IN PHASE I, WE WILL CONSTRUCT HGH/REPORTER PLASMIDS AND TO ESTABLISH THE CORRESPONDING REPORTER CELL LINES CONTAINING THESE PLASMIDS. ONCOGENE SCIENCE HAS DEVELOPED A UNIQUE ROBOTIC TECHNOLOGY TO IDENTIFY MOLECULES WHICH ACT AS SPECIFIC MODULATORS OF GENE TRANSCRIPTION. THE AUTOMATED SCREEN CAN ANALYZE 1,500 COMPOUNDS PER WEEK AGAINST MULTIPLE TARGET GENES. WE BELIEVE THIS APPROACH WILL LEAD TO THE IDENTIFICATION OF NOVEL LEAD COMPOUNDS WITH A POTENTIAL TO BE DEVELOPED INTO POTENT HGRF AGONISTS.