observer

Prague - has concentrated on a substance called vascular endothelial
growth factor (VEGF), a natural body chemical that stops arterial cell
division.

Sometimes, however, VEGF does not act quickly enough and too many
cells are produced. These form mounds inside the artery. Cholesterol
floating through arteries sticks to the mounds. White blood cells also
get trapped there.

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The mound turns into a major blockage, the artery closes, and
eventually a stroke or a heart attack is triggered.

'The root of the problem lies with those initial mounds,' said
Yla-Herttuala. 'If we stop the mounds in the first place, then
cholesterol will have nothing to stick to and no blockages will
occur.'

The solution, said Martin, is to persuade the body to make extra VEGF.
'It is a natural substance, but in later life - for as yet unknown
reasons - we stop producing enough.'

To get round this problem, Martin's team has taken the gene for VEGF
and inserted it into a virus. These genetically modified viruses are
then used to infect artery cells, in the process carrying extra VEGF
genes into them.

The cells, armed with extra VEGF, produce more growth factor and this
triggers a rapid cutback in cell production.

'This has an immediate clinical use,' added Martin. 'During surgery,
when two blood vessels are stitched together, excess arterial cells
are produced and these can cause serious blockages - a major problem
for surgeons and patients.'

Martin - who set up a biotechnology company, the London-based Ark
Therapeutics, last year to fund his work - has created a collar which
contains modified viruses that surrounds a newly joined artery and
stimulates its cells to produce VEGF, curtailing their growth.

Clinical trials of the VEGF collars began last year and are scheduled
to continue for another 12 months. 'So far, everything has worked
extremely well,' said Martin. 'We are showing that VEGF can greatly
reduce the build-up of mounds of cells inside an artery.'

But using genetically modified viruses to deliver VEGF is only useful
for medical operations. As a means of delivering a preventative drug
to be taken regularly by millions of people, it is extremely
impractical.

'We need to devise a version that can be taken orally,' said
Yla-Herttuala. 'That is the only practical solution: a pill that can
be swallowed once or twice a week.'

Simply giving people capsules of VEGF would not work, however. Acids
in the gut would destroy growth factor molecules long before they got
into the blood.

'We have to pinpoint the active part of VEGF - the bit that fits into
a cell and triggers the release of the chemicals that stop arterial
mounds building up,' he said.