Common Drug May Revolutionize Treatment of Strokes and Heart Attacks

The recently discovered effects of a common over-the-counter drug may have important implications for the treatment and prevention of heart attacks and strokes, according to a study published Sunday in the journal Nature Biotechnology.

Through an innovative drug screening process designed to find compounds that target cellular energy metabolism, a team of researchers at Harvard-affiliated Massachusetts General Hospital found that the drug Meclizine has the potential to revolutionze the way doctors treat strokes and heart attacks.

“This is the first time nutrient sensitized screening has been used to identify drug targets in human cells,” said Vishal M. Gohil, an instructor in medicine at Harvard Medical School and co-lead author of the study. “People never thought it was possible to do this approach on the scale we did.”

The researchers focused on studying the biology of mitochondria, the powerhouses of the cell where the biochemical processes of energy production occur. Human cells have the ability to switch between mitochondrial respiration and glycolysis, and do so many times throughout the day to match the body’s energy needs with its activities.

“We were interested in trying to better understand how this switching takes place under normalcy, because we thought there might be some diseases characterized by a bias in one direction,” said Vamsi K. Mootha, the lead author of the study and an associate professor of systems biology at HMS.

The team screened nearly 3,700 compounds—over a third of all FDA-approved drugs—to determine those that could effect a shift from respiration to glycolysis. In the process, researchers discovered that Meclizine can inhibit mitochondrial respiration by shifting cellular metabolism—a promising find for the treatment of heart attacks and strokes.

“Research has shown that if you modulate respiration a little bit you get a lot of protection from ischemic [related to restriction in blood supply] injuries like strokes and heart attack,” Gohil said.

“Our hypothesis predicted that these compounds that inhibit respiration should be protective in ischemic events and that is exactly what we found,” Gohil added.

Although Meclizine has been used as an over-the-counter treatment for nausea and vertigo since the 1950s, doctors had never before recognized its additional therapeutic potential.

But further research must be conducted with animal models and humans to better understand the drug’s effects, according to Sunil A. Sheth ’04, a co-lead author of the study.

“While this research could be useful for patients at higher risk for ischemia, we still need to nail down how exactly this drug is causing cells to rewire their metabolism,” Sheth said. “Our findings are very exciting, but so far we have only done animal trials and remain cautiously optimistic about applications in humans.”

The study was funded by grants from the American Diabetes Association and the Smith Family Foundation.