Grant: Project Grant

Thrombosis- clotting of the blood in blood vessels- is the leading cause of death in Canada and in the Developed society. Blood clot formation in arteries (blood supply vessels) is a major cause of majority of heart attacks and stroke. Blood clot in veins (venous thromboembolism (VTE)) is the third leading cause of death in world after heart attacks and stroke, and is one of the leading cause of death in patients with cancer. Current treatment of these diseases includes the use of drugs which can prevent platelet (a type of blood cell) activation and aggregation, and the use of anticoagulants (blood thinners). However, none of these therapies are perfect due to inherent bleeding side effects associated. Importantly, none of these treatments target the fundamental cause of pathological thrombosis in veins and arteries. Recent studies discovered that biomolecules such as polyphosphate released by platelets and extracellular nucleic acids released by the damaged or activated cells in the blood vessels initiate blood coagulation and cause pathological thrombosis. Thus, in this proposal we are developing novel molecules that can directly neutralize the activity of these potent thrombus generating polyanionic biomolecules by selectively binding them and forming a complex thereby preventing the thrombus formation. This novel drug molecules will also have no or minimal bleeding side effects unlike the current drugs used in the management of thrombosis. This research is based on a recent discovery of a patented novel class of dendritic polymeric inhibitors in our laboratory. This novel therapeutic approach will change the way clinicians treat the patients suffering from blood clot problems and will save the lives of millions of people, and improve their quality of life.