Activated platelets targeted drug therapy

Summary Developing a novel targeted fibrinolytic drug that is directed against activated platelets. Fibrinolysis is a valuable alternative for treating myocardial infarction when an invasivesurgical procedure is not available in a timely fashion.

Project Details

Acute thrombosis causes vessel occlusion resulting in ischemic complications, such as myocardial infarction and stroke, and is a major cause of death and disability worldwide. Fast and effective breakdown of thromboses is crucial to reduce injury and improve recovery.

Fibrinolysis is a valuable alternative for the treatment of myocardial infarction when invasive surgical procedure is not available in a timely fashion. For acute ischemic stroke, fibrinolysis is the only treatment option with a very narrow therapeutic window. However, clinically approved thrombolytics have significant drawbacks, including bleeding complications due to the high systemic concentration required. Thus their use is highly restricted leaving many patients untreated.

This project would focus on the development of a novel targeted fibrinolytic drug that is directed against activated platelets. The use of small recombinant antibodies for diagnostic molecular imaging and targeted drug delivery is well established in our lab.

When thrombosis occurs, platelets are activated and aggregate together to form a thrombus. Our targeted fibrinolytic drug will locate these activated platelets and accumulate at the site of the clot where they will act to break the clot down. This allows a high potency of drugs for efficient and safe thrombolytic treatment. Due to the targeting properties, we can reduce the concentration of drugs needed, which would also enable us to eliminate the current bleeding complications associated with the clinically used fibrinolytic drugs.

Significance: This project will develop and test a novel fibrinolytic agent with the capability to overcome the current limitations in thrombolytic therapy associated with the risk of bleeding complications. It has the potential to break the fatal link between increased fibrinolytic potency and bleeding complications.