Project summary

The development of a blood clot in the cerebral circulation (ischaemic stroke) is the third most common cause of death and the most common cause of adult disability globally. The central goal of stroke therapy is the prompt reperfusion of occluded blood vessels to minimise tissue death, with administration of “thrombolysis” (intravenous recombinant tissue-type plasminogen activator, rtPA) – the only clinically approved drug available to stroke patients. Despite this, the use of rtPA is associated with significant side effects, limiting its widespread use. We are working on several novel approaches to improve upon existing stroke therapies, making them safer and more effective.

While it is broadly accepted that restoration of blood flow to the brain will limit the progression of cell death and improve patient outcome after stroke, there is evolving evidence that reopening the blocked artery (recanalization) does not always lead to reperfusion of the small vessels of the brain. Critically, failure of cerebral reperfusion correlates with worse prognosis for stroke patients.

Project team

Papers

1. Jackson SP and Schoenwaelder SM. Nat Rev Drug Discov, October, 2(10): 775-789, 2003.

2. Jackson SP, et al, Nat Med, 11(5):507-514, 2005.

3. Schoenwaelder SM, et al, J Biol Chem, 282(39):28648-58, 2007.

4. Simone M Schoenwaelder, et al, J Biol Chem, 285(4):2886-2896, 2010.

5. Andre L. Samson, et al, Sci Rep. 2015 Nov 4; 5:16171. doi: 10.1038/srep16171.

6. Andre L Samson, et al; Blood 2017, Dec 7;130(23):2453-2462. doi: 10.1182/blood-2017-06-789032. Epub 2017 Oct 26. Selected as a Plenary Paper

7. Shaun P. Jackson and Simone M. Schoenwaelder, J Thromb Haemost, 10(10): 2123-2126, 2012.

Other Thrombosis projects

Developing a novel preclinical ischaemic stroke model

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The powerful enzyme Thrombin is by far the most robust activator of platelets and blood clotting (coagulation) in both physiological haemostasis and pathological thrombotic response.

Solving a sticky clotting problem in diabetes

The leading cause of death in people with diabetes is cardiovascular disease, with up to 70% of deaths relating to the development of blood clots supplying the heart (heart attack) or brain (ischemic stroke).