Acute ischaemic stroke (stroke) is the third most-common cause of death and a leading cause of disability worldwide. The majority (85%) of strokes are caused by blood clots that reduce/stop flow of blood to the brain. The mainstay of stroke treatment is therefore to quickly remove these clots and restore blood flow to the brain, to prevent extensive and permanent damage to brain tissue.
“Clot-busting” drugs that dissolve the blood clot (rtPA) are currently used to treat patients with stroke. However, while administration of rtPA (“Thrombolytic therapy”) is the only drug clinically approved for stroke therapy, significant limitations undermine its clinical effectiveness. These include a low success rate in dissolving clots forming in larger vessels, a tendency to promote clot reformation, and an increased risk of life-threatening bleeding. Given that any bleeding in the brain can be catastrophic, strict eligibility criteria surround the use of rtPA for stroke, such that it is only administered in 13% of all stroke patients, with less than half of these achieving a good therapeutic outcome.
A significant problem associated with thrombolysis, is that as a result of breaking down the blood clot, rtPA inadvertently releases thrombin, the very enzyme responsible for clot formation in the first instance. This is thought to be responsible in part for promoting re-clotting events. While the simple addition of an anti-thrombin or anticoagulant drug – of which there are many clinically approved – has the potential to prevent this “re-clotting” phenomena, all existing anticoagulants cause excessive bleeding and are therefore unsafe for use in the treatment of stroke.
We have identified a novel anticoagulant protein found in the saliva of blood feeding insects, which has the unique ability to block clot formation without causing significant bleeding. We will use state-of-the-art preclinical models established in our lab to examine whether this novel anticoagulant can be used to improve the safety and effectiveness of thrombolytic therapy, leading to improved stroke outcomes.