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Heart Drugs May Help Shield Brain Cells From Stroke

Digoxin and digitoxin show early promise in rat studies

TUESDAY, June 20, 2006 (HealthDay News) -- New laboratory research suggests that digoxin and digitoxin, two widely used heart drugs, could protect the brain from damage during a stroke.

The findings are preliminary, and scientists have only tested the drugs on the brain cells of rats. However, confirming the drugs' effects in human trials could lead to a powerful new weapon against stroke, the researchers said.

Despite billions of dollars spent on research, "not a single stroke drug has come out that protects neurons from the damage caused by stroke. There's this amazingly huge need for a protective drug," noted senior researcher Donald Lo, director of the Center for Drug Discovery at Duke University Medical Center in Durham, N.C.

According to the American Heart Association, more than 700,000 Americans are diagnosed with stroke each year, with stroke rehabilitation costs topping $50 billion annually.

In search of a new stroke treatment, Lo and colleagues tested thousands of existing drugs by injecting them into dishes containing slices of rat brains. Because scientists can simulate the effects of stroke in brain cells, they can save money by not having to test the drugs on live rats.

Nearly all the drugs tested failed to prevent neurons from dying. But a chemical found in digoxin and digitoxin worked, according to the study, which is published in this week's issue of the Proceedings of the National Academy of Sciences.

The chemical, known as neriifolin, protected the cells of the brain slices from damage for six hours or more, the researchers reported. The chemical -- one of a class of molecules called cardiac glycosides -- also appeared to prevent brain damage in live rats.

Currently, no drug has been shown to directly protect sensitive neurons during a stroke, said Lo, who is also an associate professor of neurobiology at Duke. One commonly well-known stroke drug, tissue plasminogen activator, or tPA, is a "clot buster" that breaks open blockages in blood vessels. But tPA only works if given within a few hours after a stroke.

Digoxin is a common heart drug used to treat heart failure and atrial fibrillation, a kind of irregular heartbeat. Digitoxin is also used to treat heart problems, but it's used less now than in the past, Lo said.

"The most exciting outcome would be if digoxin itself could be used in treatment of stroke," Lo said. "But there are a lot more studies that need to be done before that is tested in humans."

Another expert agreed that a pinch of caution is warranted.

"Lots of agents have been found useful as neuroprotectants in mice and rats and did not pan out to work in people for various reasons," said Dr. Rafael H. Llinas, medical director of neurology at Johns Hopkins Bayview Medical Center in Baltimore.

Still, it's possible that a treatment might be able to protect the brain from the effects of a stroke, or "at least prolong the period when the brain is able to tolerate not getting enough oxygen, blood and energy," he said.

Llinas noted, for example, that some people survive being trapped under the ice in a frozen lake for a significant period of time. "Then, when they are removed and resuscitated, they are neurologically intact."

Currently, he said, researchers are trying to develop a treatment that both protects the brain, perhaps by slowing its function, but doesn't put the heart in danger.

More information

Learn more about stroke from the American Stroke Association.

SOURCES: Donald Lo, Ph.D., associate professor, neurobiology, and director, Center for Drug Discovery, Duke University Medical Center, Durham, N.C.; Rafael H. Llinas, M.D., assistant professor of neurology, and medical director, Bayview Neurology, Johns Hopkins Bayview Medical Center, Baltimore; June 19-23, 2006, Proceedings of the National Academy of Sciences
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