New Drug May Reduce Heart Attack Damage

Cardiovascular disease researchers have discovered a compound that shows promise as a drug to reduce the extent of damage caused to the heart muscle during a heart attack.

Investigators at Stanford University (Palo Alto, CA, USA) and at Indiana University (Indianapolis, IN, USA) identified mitochondrial aldehyde dehydrogenase 2 (ALDH2) as an enzyme whose activation correlated with reduced ischemic heart damage in rodent models. This finding prompted the search for drug candidates that could activate ALDH2.

The researchers reported in the September 12, 2008, issue of the journal Science that by employing a high-throughput screening assay they were able to show that the synthetic compound Alda-1 directly bound ALDH2, enhanced its activity, and reduced cardiac damage by 60% when injected directly into the hearts of live healthy rats five minutes before the induction of a simulated heart attack caused by blockage of blood flow to the heart.

"The idea was to find a small molecule that could bypass the signaling process and activate the enzyme directly," said contributing author Dr. Thomas D. Hurley, professor of biochemistry and molecular biology at Indiana University. "Although the Alda-1 molecule reduced heart tissue damage in laboratory tests, years of work will be necessary to refine the compound into a version that would be potentially effective and safe for human use."

That benefit could extend to about 40% percent of people of East Asian descent who carry a mutated form of the ALDH2 enzyme, which puts them at increased risk of cardiovascular damage.

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Stanford University
Indiana University