New Clot Busting Drug Could Improve Stroke Treatment

A new clot busting drug developed by scientists at the University of Manchester is able to effectively break down blood clots in the brains of mice that are resistant to current drugs, according to research BHF funded and published in the journal Blood. The scientists say that the findings could open the door for a safer and more effective stroke treatment.

A stroke happens when the blood flow to part of the brain is cut off. Most strokes are caused by a blood clot blocking an artery carrying blood to the brain (an ischaemic stroke) meaning brain cells don’t get the oxygen they need to work. Treatments for this type of stroke focus on removing the blood clot to restore blood flow to the brain.

The researchers found that the drug they’ve developed, called caADAMTS13, was effectively able to break down blood clots in the brains of mice who had had a stroke. They also found signs that it may have a beneficial effect on the immune response that a stroke triggers.

Current treatments don’t work for everyone

Alteplase is currently the only clot busting drug approved to treat patients who have an ischaemic stroke. While it works for many patients, it’s less able to break down clots which are rich in Von Willebrand Factor, a protein that plays a crucial role in blood clot formation. Around 50 per cent of clots are rich in Von Willebrand Factor.

The drug developed by the Manchester team specifically targets Von Willebrand Factor. It is a modified version of the ADAMTS13 enzyme, which occurs naturally in the body. The researchers compared the effectiveness of their drug against the ‘standard’ version of the ADAMTS13 enzyme.

They found that, when it was given to mice one hour after a stroke, caADAMTS13 was more effective at breaking down Von Willebrand Factor, reducing levels of the protein five times more quickly than ADAMTS13.

The drug also prevented neutrophils, a type of white blood cell, from entering the brain tissue that had been starved of oxygen. This process is thought to damage brain cells, so preventing this from happening could further help to reduce the amount of damage a stroke causes.

The researchers now need to show whether caADAMTS13 is effective if it’s given after a longer period of time has passed since the stroke and whether it has any potential side effects. Once they’ve investigated this they hope to move on to clinical trials to test its effectiveness in humans.

New treatments are sorely needed

Professor Metin Avkiran, BHF Associate Medical Director, 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.”