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Drugs designed by nature could prevent heart attacks and blood clots

27 August 2009

Scientists have tapped into nature's medicine chest to develop a new drug that controls blood flow and prevents clotting.

Their discovery is 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 UK's Centre for Ecology & Hydrology (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 long-lasting than the direct thrombin inhibitors currently on the market.

Professor Nuttall, Director of CEH, explained, "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."

Prof Kini said, "Driven by hundreds of millions of years of evolution, ticks have developed very potent and specific molecules that stop the blood clotting and enable their blood-feeding life style and survival. 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."

Dr. Koh added, "We 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. 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 could 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. The NERC 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 when it will make a real difference to the man in the street."

Further information

NERC Press Office
Natural Environment Research Council
Polaris House, North Star Avenue
Swindon, SN2 1EU
Tel: 01793 411561
Mob: 07917 557215

Kate Groves
CEH press office
Tel: 01491 692358
Mob: 07920 727653

Adela Štrpková
Slovak Academy of Sciences
Tel: +421 2 5751 0154

Fun Yip
National University of Singapore
Tel: +65 6516 1374

Notes

1. The Centre for Ecology & Hydrology (CEH), a public sector research establishment, is the UK's centre of excellence for integrated research in land and freshwater ecosystems and their interaction with the atmosphere. CEH is part of the Natural Environment Research Council and employs over 450 people at five major sites in England, Scotland and Wales with an overall budget of about £35m. CEH tackles complex environmental challenges to deliver practicable solutions so that future generations can benefit from a rich and healthy environment.

2. The Natural Environment Research Council (NERC) funds world-class science, in universities and its own research centres, that increases knowledge and understanding of the natural world. It is tackling major environmental issues such as climate change, biodiversity and natural hazards. NERC receives around £400m a year from the UK government's science budget, which is used to provide independent research and training in the environmental sciences.

3. The National University of Singapore (NUS), a leading global university centred in Asia, is Singapore's flagship university which offers a global approach to education and research, with a focus on Asian perspectives and expertise. NUS has 14 faculties and schools across three campuses. Over 30,000 students from 100 countries enrich the community with their diverse social and cultural perspectives. Well-known for its research strengths in engineering, life sciences and biomedicine, social sciences and natural sciences, NUS shares a close affiliation with three Research Centres of Excellence, 21 university-level, 16 national-level and more than 80 faculty-based research institutes and centres.

4. The Slovak Academy of Sciences (SAS) is the main scientific and research institution in Slovakia fostering basic and strategic basic research. It was founded in 1942, closed after WWII, and then re-founded in 1953. Its primary mission is to acquire new knowledge of nature, society and technology, specifically targeted at ensuring scientific basis for the advancement in Slovakia. It comprises 58 scientific institutes and 13 ancillary institutions. The SAS edits 44 scientific and scholarly journals and 100-120 monographs per annum. Moreover, 41 scientific and scholarly societies, which associate scientists and scholars from various disciplines, are affiliated with SAS.

Press release: 17/09

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