Breakthrough in research to halt fatal blood clots

BRITISH scientists have won a global race to determine the structure of a human protein implicated in the deaths of 1,000 people a day who suffer lethal blood clots.

The find, disclosed today in the journal Nature, will help pharmaceutical companies design a new generation of clot-busting drugs, estimated to be worth pounds 1bn a year, for people at risk of stroke and heart attacks.

Several teams of researchers from around the world have been trying to determine the detailed three-dimensional structure of 'tissue factor', a protein which resides on the outside of blood vessels that triggers the complex set of events resulting in the formation of a blood clot.

Scientists from the universities of Oxford and Edinburgh and the Royal Postgraduate Medical School at Hammersmith Hospital, in west London, are the first to publish the structure of tissue factor, although they are keeping details secret until Genentech, the US drug company with rights to exploit their work, has had time to capitalise on the discovery.

Professor Ted Tuddenham, a Medical Research Council scientist at Hammersmith, said: 'Up to now we have been guessing how this tissue factor works. Now the curtain has been raised and we can suddenly see its shape and decipher how it works.'

Nearly 500 people a day die in the UK as a result of coronary artery disease involving the formation of clots within a blood vessel. At least as many again die as a result of blood clots elsewhere in the body, such as the blood vessels serving the brain, Professor Tuddenham said.

Clots form as a result of a cascade of biochemical reactions which start with tissue factor binding to a clotting factor circulating in the blood stream. Normally this occurs only when a blood vessel is ruptured, but it can also happen when arteries become clogged with fatty deposits, which leads to thrombosis.

Now that the structure of tissue factor is known, scientists will be able to design drugs that can block its role in the formation of a clot and produce a safer generation of clot-busters for people at risk of heart attacks and strokes.

Professor Tuddenham said that cancer patients and people suffering septic shock - when bacteria infect the bloodstream - will also benefit because they too are at risk of blood clots.

Bill Boys, a Wellcome Trust research fellow at Edinburgh University, said finding the protein was akin to finding the stream at the top of a waterfall. 'We now have knowledge in atomic detail of the molecule that causes blood to clot and should be able to monitor the action of that molecule with drugs that can be designed rather than relying on trial and error.'