Leukemia pill may improve stroke treatment: study

CHICAGO Sun Jun 22, 2008 2:55pm EDT

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CHICAGO (Reuters) - A highly effective leukemia pill may reduce complications and boost the effectiveness of a treatment for the most common type of stroke, an international team of researchers said on Sunday.

Studies in mice showed giving Gleevec or imatinib, a drug made by Novartis AG, significantly reduced bleeding in the brain associated with the clot-busting drug known as tissue plasminogen activator or tPA.

It also appeared to extend the time window in which the drug could be given, they said.

"You potentially could reduce the amount of side effects associated with tPA and increase the population that could receive it," said Daniel Lawrence of the University of Michigan Medical School, whose findings appear in the journal Nature Medicine.

Lawrence worked with researchers from the Karolinska Institutet in Stockholm, Sweden, which plan to start testing the drug combination in humans in the next few months.

The clot-buster tPA is used to dissolve blood clots in ischemic stroke, a type of stroke triggered when a blood clot impedes blood flow to the brain. These strokes account for 80 percent of the 15 million strokes that occur each year worldwide, according to the World Health Organization.

When given within the first three hours of a stroke, tPA can chew up the clot and significantly reduce death and disability. But tPA has two major drawbacks: it can cause blood to leak into the brain and it must be used within three hours after the start of the stroke.

And because the drug causes bleeding, it can not be used in a more rare type of stroke known an intracerebral hemorrhage, which is caused when a blood vessel in the head ruptures.

Lawrence said they now have a better understanding of why tPA causes bleeding. He said when tPA seeps into the brain through stroke-damaged vessels, it appears to act on a protein involved in blood vessel formation called PDGF-CC and the PDGF-alpha receptor that it binds to.

This process weakens the blood brain barrier -- a complex mechanism that protects the brain from toxins in the blood -- making blood vessels porous and vulnerable to leaks. Gleevec, which blocks the PDGF-alpha receptor, appears to counteract this effect.

The researchers tested this theory in a series of studies in mice. In one, they induced strokes and an hour later gave some of the mice a dose of Gleevec. Mice that got the drug had 33 percent less leakage. They also had 34 percent less damage to the brain 72 hours later.

They then tested Gleevec as a pre-treatment before giving tPA to protect against bleeding in the brain. They gave Gleevec to mice one hour after the stroke began, but waited another four hours before giving tPA, long past the typical three-hour treatment window for tPA.

They measured levels of the blood protein hemoglobin in the brain to test for bleeding. Mice given Gleevec had 50 percent less hemoglobin than those not given Gleevec.

The study suggests Gleevec may help prevent blood vessel leakage associated with tPA and could extend the time window in which it can be used, If the findings are confirmed in humans, Lawrence said it could give patients and doctors more time.

"It could have a huge benefit," he said.

(Editing by Todd Eastham)

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