A novel ‘clot-busting’ drug is able to effectively restore blood flow in the brains of mice, opening the door for a safer and more effective stroke treatment.
The compound – an enzyme called caADAMTS13 – could dissolve clots in patients that are resistant to current treatment, the study from the University of Manchester has revealed.
tPA – currently used by doctors in the acute phase of a stroke – works for many patients, however, it is not able to break down clots which are rich in Von Willebrand Factor (VWF), a large string shaped protein molecule which plays a crucial role in clot formation.
Around 50 per cent of all clots are rich in VWF – which tethers circulating clotting cells called platelets at sites of clot formation – and are resistant to tPA.
The team examined the efficacy of the drug in mice and compared it with the wildtype variant of the enzyme – called wtADAMTS13 that occurs naturally in the body.
When given one hour after a stroke, the new drug significantly reduced VWF by dismantling its long chains – five times more quickly than the wildtype variant achieved.
The drug also prevented a type of white blood cell called a neutrophil from entering the brain tissue starved of blood supply and thought to be a cause of the damage to brain cells.
Stroke is caused by a reduction in blood flow to the brain, which most frequently results in loss of movement, problems with speech and other symptoms in the patient.
The reduced blood flow is most often caused by a blood clot that lodges in the narrow blood vessels that supply the brain, which means the cells of the brain don’t get the energy they need to work.
If blood flow is not quickly restored the brain cells will die leading to permanent brain damage and, if severe, death.
Now, through the study of the novel compound – which is patented by the team and funded by the British Heart Foundation – stroke survivors can have fresh hope of recovery.
Professor Stuart Allan from the University of Manchester, co-author of the study and co-director of the Geoffrey Jefferson Brain Research Centre, said: “Our novel drug is able break down the blood clots that are resistant to the current treatment tPA. In doing so, more stroke patients could show recovery of function than at present.
“Clearly there is still some way to go, and we need to know if the drug is effective a period of time after the stroke has occurred – with less risk of haemorrhage.
”We are optimistic that we will be able to show this drug can to do that; once we have, we hope to move onto human trials. It’s very exciting.”
Professor Metin Avkiran, associate medical director at the British Heart Foundation, said: “The majority of strokes, which can have such devastating consequences, are caused by a blood clot cutting off blood supply to part of the brain.
“With over 100,000 strokes in the UK each year, new treatments are sorely needed to improve outcomes for patients.
“These promising findings suggest that drugs that target Von Willebrand Factor (VWF) have the potential to safely and effectively dissolve blood clots that resist currently available therapies.
“More research will be needed to understand whether these results in mice can be replicated in humans, and whether this can help to improve survival and recovery for stroke patients.”
