New class of drugs may cut cardiovascular disease risk

Washington, August 7

Scientists have designed a potential new class of drugs that may reduce the risk of cardiovascular disease by targeting a specific microbial pathway in the gut.

Unlike antibiotics, the new class of drugs prevents microbes from making a harmful molecule linked to heart disease without killing the microbes, which are part of the gut flora and may be beneficial to overall health.

The study, published in the journal Nature Medicine, found that the new drugs reversed two major risk factors for cardiovascular disease—increased platelet responsiveness and excessive clot formation—in mice. They did so by lowering levels of TMAO (trimethylamine N-oxide), a gut bacteria byproduct that forms during digestion, said researchers from Cleveland Clinic in the US.

High levels of TMAO in the blood have been shown to be a powerful tool for predicting future heart attack, stroke and death risks, they said.

TMAO is produced when gut bacteria digest choline, lechithin and carnitine, nutrients that are abundant in animal products such as red meat and liver, they said.

Choline is also abundant in egg yolk and high-fat dairy products.

The group demonstrated that a new series of inhibitors, called mechanism-based inhibitors, potently interrupt the gut microbial pathway that produces TMAO.

Because the compounds are structurally similar to choline (called analogues), the bacterial cells are "tricked" into taking them up as nutrients.

Once transported into the microbe, the inhibitors then block the production of TMAO by inactivating a specific gut microbe enzyme called cutC (choline utilization protein C).

"To our knowledge, this is the most potent therapy to date for 'drugging' the microbiome to alter a disease process," said Stanley Hazen from Cleveland Clinic.

"In addition, gut bacteria are altered but not killed by this drug, and there were no observable toxic side effects," said Hazen.

"The approach developed could potentially be used to target other gut microbial pathways. We look forward to advancing this novel therapeutic strategy into humans," he said. PTI