Clotbuster drug is new hope for stroke treatment
A new clotbusting drug tested on mice has been shown by University of Manchester scientists to be significantly better at treating ischemic stroke than existing therapies.
The compound, developed by the scientists and known as caADAMTS13, could be a breakthrough for patients who have brain blood clots with an overabundance of platelets- the tiny cell fragments that help form clots and are often not treatable by existing therapies.
The study, funded by a British Heart Foundation 4-Year PhD Studentship Program and The University of Manchester Innovation Factory is published in the leading journal in the field, Stroke.
It is the first potential new treatment for stroke in the UK since the clotbusting drug recombinant tissue plasminogen activator (rtPA) was licensed in September 2002.
According to existing research, rtPA is only effective in as few as 10% to 35% of patients and is associated with a significant risk of bleeding.
Another clotbuster called Tenecteplase (TNK), a variant of rtPA, was recently approved for the treatment of acute ischemic stroke in the United States but has similar limitations to rtPA.
Both rtPA and TNK have similar efficacy and risk of haemorrhage.
Von Willebrand Factor (VWF), a protein involved in blood clotting, helps platelets stick to damaged blood vessels and form the structure of blood clots.
The greater the proportion of platelet and VWF components in a clot, the less effective rtPA is in dissolving it.
The scientists investigated an alternative strategy which utilises caADAMTS13, an enzyme that reduces the size of VWF and helps break down blood clots.
In previous mouse studies they have already shown that caADAMTS13 improves cerebral blood flow, reduces damage in the brain, reduces the depositing of both platelets and a clot promoting protein called fibrin, as well displaying anti-inflammatory properties.
However, until now, a head to head comparison with the existing therapies of rtPA and TNK had not been carried out.
The scientists directly compared caADAMTS13 with rtPA and TNK in mice with a cerebral artery blockage from platelet and VWF rich clots, to mimick rtPA-resistance.
They found that the restoration of cerebral blood flow 1 hour after treatment was the greatest in the mice treated by caADAMTS13 and that at 24 hours the caADAMTS13 mice had reduced brain damage.
Our findings show that the compound we developed, called caADAMTS13, is more effective than current stroke treatments. That is why it is tremendously exciting that this compound could one day meet an unmet clinical need for stroke patients
Lead author Lucy Roberts, from The University of Manchester, said: 鈥淲hen someone has an acute ischemic stroke, doctors need to quickly remove the clot blocking cerebral arteries in the brain.
鈥淭o avoid severe and potentially life-threatening complications, the need to act fast is acute. Unfortunately, current treatments are only sometimes effective.
鈥淗owever, our findings show that the compound we developed, called caADAMTS13, is more effective than current stroke treatments
鈥淭hat is why it is tremendously exciting that this compound could one day meet an unmet clinical need for stroke patients.鈥�
Co-author and principle investigator Professor Stuart Allan from The University of Manchester said: 鈥淲e know that removing blood clots can improve outcomes in stroke and that current treatments don鈥檛 always work.
鈥淭herefore, the approach is proven to work and we just need better drugs that can break down all types of blood clots. We think caADAMTS13 may allow this to happen.鈥�
Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, said: "A stroke is a medical emergency. For every minute blood flow to the brain is disrupted during a stroke, millions of nerve cells can become damaged and die. Stroke remains the single biggest cause of severe disability in the UK and we urgently need new treatments.
鈥淢ore research will be needed to understand how these early results in mice can be translated to humans, but this study gives us a promising glimpse into a future where the compound caADAMTS13 could potentially be developed as a new therapy to safely and effectively dissolve blood clots in the brain.鈥�
The paper Comparison of the Novel Thrombolytic Constitutively Active ADAMTS13 With Clinical Thrombolytics in a Murine Stroke Model , DOI: 10.1161/STROKEAHA.125.050848, is available
- The video animation illustrates the formation of a clot. Please credit the .
- For the image of the brain, please credit the .