22 November 2021

British scientists have developed a drug to break down blood clots in the hope it will be an effective therapy for stroke patients, it has been announced.

The treatment was created by a team at the University of Manchester led by Professor Stuart Allan and Dr Ingo Schiessel. It is based on the enzyme ADAMTS13, which is secreted into the blood and reduces the action of von Willebrand factor, a protein involved in blood clotting.

They explained in the journal Blood last week that recent advances in understanding of ADAMTS13 "have rejuvenated the possibility of its use as a thrombolytic therapy".

The team created a variant of the enzyme, called caADAMTS13, which is permanently active. caADAMTS13 was tested and found to “greatly enhance thrombolytic activity in two [mouse] models of ischaemic stroke”.

When given to mice one hour after artificially induced thrombus formation, caADAMTS13 significantly reduced the von Willebrand factor protein in the middle cerebral artery. It also reduced platelet aggregation and improved blood flow to nearby tissue.

“The caADAMTS13 variant represents a potentially viable therapeutic option for the treatment of acute ischaemic stroke, amongst other thrombotic indications, due to its enhanced in vitro and in vivo activities,” the authors write.

Professor Allan said: “Our novel drug is able to break down the blood clots that are resistant to the current treatment tPA [recombinant tissue plasminogen activator]. 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 do that; once we have, we hope to move onto human trials. It’s very exciting.”

Source:

South K, Saleh O, Lemarchand E, Coutts G, Smith CJ, Schiessl I, Allan SM. (2021) “Robust Thrombolytic and Anti-Inflammatory Action of a Constitutively Active ADAMTS13 Variant in Murine Stroke Models.” Blood, doi: 10.1182/blood.2021012787

Link: https://ashpublications.org/blood/article/doi/10.1182/blood.2021012787/477972/Robust-Thrombolytic-and-Anti-Inflammatory-Action

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