Compound Could Reduce Heart Attack Damage

THURSDAY Sept. 11, 2008 -- A newly developed molecule holds the promise of reducing the damage done by heart attacks and a number of diseases, including Alzheimer's and Parkinson's, researchers report.

Oh, it might cure hangovers, too, but the scientists working on it prefer to downplay that aspect of their research.

The molecule is called Alda-1, although its chemical name is "quite a bit more complicated," said Thomas D. Hurley, a professor of biochemistry and molecular biology at Indiana University, who is working with researchers at Stanford University on the project. It has been given that name, because it activates an enzyme called aldehyde dehydrogenase 2 (ALDH2), best known until now for its role in the processing of alcohol.

ALDH2 was unexpectedly found to play a role in protecting the heart from damage, said Daria Mochly-Rosen, a professor of chemical and systems biology at Stanford, and lead author of a report in the Sept. 12 issue of Science. In animal studies led by Mochly-Rosen, the enzyme was found to reduce the tissue damage done by unstable oxygen products called free radicals.

That finding helps explain a long-known phenomenon in which moderate drinkers tend to have less severe heart attacks than teetotalers. Alcohol, in small amounts, preconditions the heart to resist damage, but until now, the reason for the preconditioning has been unknown.

The Stanford team screened a large number of compounds to find one that would increase the activity of ALDH2. They called on Hurley for help, because "he has spent his career on this enzyme, he knows a lot about the structure of the enzyme and how it works," Mochly-Rosen said.

Much of the research on ALDH2 has been done in Japan and China, because about 40 percent of Asians carry a variant form of the gene that makes a relatively inactive enzyme, Hurley said. "It gives rise to a number of susceptibilities, including intolerance to ethanol, beverage alcohol," he said.

That intolerance also has medical implications. A number of studies have shown that people carrying the gene variant respond less to the nitroglycerin therapy that is a basic part of heart disease treatment, Hurley said.

And the activation of ALDH2 activity has the potential for much wider clinical applications. Free radical damage is a major feature of Alzheimer's, Parkinson's and other diseases, Mochly-Rosen noted.

If it fulfills its promise, Alda-1 could be given to someone in a situation where the heart is subject to free radical damage, Hurley said. It could help recovery from heart surgery, for example. The ultimate hope is that it can be given to prevent such damage.

That would require a long series of trials, and the candidate drug emerging from them might not be Alda-1, Mochly-Rosen said. With Hurley, the Stanford researchers are looking at chemical relatives that might be more effective.

Given the financial requirements of such an effort, "it would require industry to step in and do it," Mochly-Rosen said.

And the thought of a pill that could be taken after a night on the town to make the morning after more bearable? "That is not something I would be very proud of," Mochly-Rosen said.

"Societal issues would come from that," Hurley said.

More information

A guide to the good and bad effects of alcohol on health is offered by the American Heart Association.

Posted: September 2008


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