Wonder drug from tick's saliva

A fully engorged female tick, species Amblyomma variegatum,from which Variegin was isolated Photo: CEHScientists from Centre for Ecology & Hydrology (CEH) are among those tapping into nature’s medicine to develop a new drug from tick saliva that controls blood flow and prevents clotting. Their discovery is now the subject of an international agreement between leading research organisations in the UK, Singapore, and Slovakia.

Dr Maria Kazimirova from the Slovak Academy of Sciences and Professor Patricia Nuttall’s team from the CEH, isolated a thrombin inhibitor (an anticoagulant, or anti-clotting agent) from the salivary glands of ticks, which they called Variegin.

They believe that the ticks secrete the anticoagulant to keep their host’s blood flowing while they feed.

Recognising the potential for this natural anti-clotting agent, the researchers teamed up with experts in snake venom peptides from the National University of Singapore.

In Singapore, Professor Manjunatha Kini and Dr Cho Yeow Koh used chemical methods to reproduce Variegin and make it more potent. They discovered that Variegin appears to be a new class of thrombin inhibitor, which may be more efficient and longer-lasting than the direct thrombin inhibitors currently on the market.

Professor Nuttall, Director of CEH, said, "By synthesising and modifying the anticoagulant our partners in Singapore were really able to understand how it works, and to improve its functions. As well as enabling blood to flow freely, we may now be able to stop the effect so that clotting is restored.

"This is an important breakthrough as it will potentially enable the development of new blood-controlling drugs with a much better performance level – and therefore fewer adverse side effects – than some of those currently available."
Professor Kini explained that during the course of evolution ticks had developed very potent and specific molecules that stop blood clotting and enable their blood-feeding lifestyle and survival.

He continued, "Although such natural compounds are close to perfection, sometimes there is still room for improvement. By understanding how Variegin works, we were able to reduce its size and at the same time improve its potency with suitable modifications."

The team now have molecules with different sizes, potency and mechanism and duration of action, providing a solid platform for further development of an anti-clotting agent. Dr Koh revealed, "One of them has 70 times more potency and long lasting anti-clotting effect than a drug that is currently available in the market."

The scientists have carried out initial tests on zebrafish to see if Variegin can prevent venous thrombosis. The tests are a model for preventing deep vein thrombosis in humans.

"The tests were a huge success and completely inhibited thrombus formation," said Professor Nuttall. "We need to do more studies like that to get Variegin into clinical trials."

This translational research could have potential applications for coronary diseases such as narrowed arteries and heart attacks, as well as deep-vein thrombosis and drug-induced blood clotting. It could be applied during major surgery to control bleeding. There is also evidence that, by controlling blood flow and clotting, the spread of some cancers could be diminished or prevented.

The international partners have filed patent applications to protect their development of this technology. They have also drawn up a commercialisation agreement through the Natural Environment Research Council (NERC), with a view to getting Variegin from the laboratory bench to the bedside. NERC's commercialisation and innovation team is now actively seeking commercial partners or licensing deals to take this forward.

Bill Barnett, business development manager, said, "This is a really exciting opportunity to take research that has potential health benefits and develop it to a stage where it will make a real difference to the man on the street."