Activated platelet-targeted drug therapy

Summary The Peter and Wang group focuses on basic and translational research covering a wide variety of themes, including cardiovascular disease, autoimmunity and cancer

Project Details

The Peter and Wang group focuses on basic and translational research covering a wide variety of themes, including cardiovascular disease, autoimmunity and cancer. We study fundamental disease mechanisms in order to define the key cells and molecules which contribute to the development or outcome of disease. Using this information, we then design, test and implement novel molecular imaging approaches using state of the art technologies (magnetic resonance imaging, ultrasound, computed tomography, positron-emission tomography and 3D fluorescence emission computed tomography). We focus on novel therapeutic approaches, such as biological therapies targeting immune cells; and theranostics, which combine both therapeutics and diagnostics into a single platform. 

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 removal/breakdown of thrombosis 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 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 need 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.