NOVEL ANTITHROMBOTIC AGENT

THIS PHASE I STUDY WILL DEVELOP A SELECTIVE ANTITHROMBOTIC WITH THERAPEUTIC USEFULNESS. THE ANTITHROMBOTIC WILL FUNCTION BY INHIBITING THE FORMATION OF THROMBIN. THROMBIN IS GENERATED FROM THE ZYMOGEN PROTHROMBIN BY THE PROTHROMBINASE COMPLEX, WHICH CONSISTS FO FACTOR XA (ASERINEPROTEASE), FACTOR VA (A COFACTOR), AND CA(2+) ASSEMBLED ON APHOSPHOLIPID SURFACE. THE PRESENT STUDY IS BASED ON THE OBSERVATION THAT PROTEOLYTICALLY INACTIVE FORMS OF FACTOR XA (FACTOR XAI) CAUSE THE FORMATION OF INACTIVE PROTHROMBINASE COMPLEXES AND LIMIT THE FORMATION OF THROMBIN. THE SPECIFIC AIM OF THIS PHASE I STUDY IS TO USE RECOMBINANTTECHNOLOGY TO EXPRESS A PROTEOLYTICALLY INACTIVE FORM OF HUMAN FACTOR XA (RXAI) THAT WILL COMPETE FOR ACTIVE FACTOR XA IN THE ASSEMBLY OF THE HUMAN PROTHROMBINASE COMPLEX. PHASE II WILL BE DIRECTED TO TESTING THE HYPOTHESIS THAT FACTOR RXAI WILL INHIBIT THE FORMATION OF THROMBI IN A SELECT NUMBER OF WELL-CHARACTERIZED ANIMAL MODELS FOR ACUTE ARTERIAL THROMBOSIS. IT IS ANTICIPATED THAT THIS RESEARCH WILL LEAD TO THE DEVELOPMENT OF A NEW FAMILY OF POTENT AND HIGHLY SELECTIVE ANTITHROMBOTIC DRUGS SUITABLE FOR THE TREATMENT OF THROMBOSIS IN SEVERAL LIFE-THREATENING CARDIOVASCULAR DISEASES SUCH AS UNSTABLE ANGINA, MYOCARDIAL INFARCTION, AND THROMBOTIC STROKE.