91av

A DRUG that talks cells out of committing suicide promises to reduce the
brain damage caused by strokes.

The compound, called AM-36, will shortly undergo human trials in Britain.
Tests in rats suggest it could reduce brain damage by as much as half if given
within six hours of a stroke.

The six-hour window is very important because many people who have just had a
stroke think it’s a headache and don’t get to hospital for at least 3 hours,
says Jennifer Callaway of Monash University in Melbourne, Australia. Her team
discovered AM-36 in collaboration with biotech companies AMRAD of Melbourne and
DevCo of Britain.

“Six hours is much later in the natural history of strokes than all previous
stroke drugs,” says David Howells, a stroke researcher from the University of
Melbourne. Having a drug that protects nerve cells up to six hours after a
stroke would be “truly wonderful”, he says.

Strokes cause a doughnut-shaped pattern of damage, Callaway says. In the
“hole” of the doughnut, where the blood supply is cut off, the cells die within
about an hour. But in the surrounding area, where there is still some blood
flow, cells survive for up to 12 hours or more. This provides a window of
opportunity for AM-36 to rescue them.

It does so in part by preventing apoptosis, or cell suicide. This seems to
play a big role in brain injuries, though it isn’t clear why
(91av, 26 September 1998, p 15).
AM-36 also prevents the release of glutamate, which in
excess amounts can damage cells. And it acts as an antioxidant, mopping up free
radicals. Studies suggest that this helps reduce damage after a stroke.

Howells thinks AM-36 has a good chance of working because it acts on all
these fronts. But Callaway warns that it could be up to 8 years before AM-36 is
available.