Research Project
7128153
DESCRIPTION (provided by applicant): Factor VIIa and tissue factor (TF) are essential proteins for the initiation of blood coagulation. Blood coagulation is initiated when cryptic TF becomes exposed on the surface of vascular cells where it can bind circulating factor VIla. The factor Vlla/TF complex catalyzes the activation of certain blood zymogens that propagate the coagulation event. The amount of circulating factor VIla has been shown to be a good indicator of hemostatic potential, and for this reason is a potential risk factor indicator for the development of cardiovascular disease. In addition, over the past decade recombinant factor VIla has become the drug of choice for treating hemophilia A and B patients who have developed inhibitors to factors VIII and IX respectively. Formation of the factor Vlla/TF complex is also the basis of specific coagulation assays. The prothrombin time (PT assay) utilizes either natural or synthetic thromboplastin reagents to initiate coagulation in-vitro. Thus in addition to its in-vivo role, TF also has in-vitro applications. Furthermore, TF is not only present in the vasculature, but also in numerous other tissues and cells including brain, lung, placenta, monocytes and tumor cells. In addition to its "normal" role in hemostasis, it is also known to be involved in the metastasis of tumor cells. The fact that factor VIla and TF play such important roles both in vivo and in vitro, indicates that rapid and direct assays for these proteins could be of great utility. At the present time, reliable assays for factor VIla and TF that can be applied to simple and well as complex biological samples do not exist. During the Phase-l project period we demonstrated the feasibility of developing sensitive fluorogenic assays that can directly measure functional factor VIla and TF in simple and complex biological systems. Phase-ll funding will be used to support the further development, refinement, optimization, validation and field-testing of these assays. It is anticipated that by the end of the Phase-ll project period these assays will be ready to market for research and pre-clinical applications.
