Novel drug reduces gut byproduct linked to heart attack, stroke
Researchers from the Cleveland Clinic have developed what could become a new class of cardiovascular drugs—one that lowers platelet responsiveness and excessive clot formation by targeting a specific bacteria byproduct in the gut.
Hyper-responsive platelets contribute to blood clots, which can lead to strokes and heart attacks.
Trimethylamine N-oxide (TMAO) is formed during digestion of certain nutrients that are abundant in the Western diet, senior author Stanley L. Hazen, MD, PhD, and colleagues wrote in Nature Medicine. Elevated TMAO has been linked to higher risks of cardiovascular disease and death, prompting a need for therapies to lower TMAO.
In a mouse study, Hazen et al. inhibited enzymes related to TMAO with an oral medication, successfully interrupting the gut microbial pathway that produces TMAO. An added bonus: the compound prevented the microbes from making TMAO but didn’t kill the microbes, which may be beneficial to overall health, according to a press release. Also, by not killing the bacteria, antibiotic resistance may be avoided.
“To our knowledge, this is the most potent therapy to date for ‘drugging’ the microbiome to alter a disease process,” Hazen said in the release. “In addition, gut bacteria are altered but not killed by this drug, and there were no observable toxic side effects.”
The researchers found a single dose of the drug—called a mechanism-based inhibitor—reduced TMAO levels for up to three days and reversed enhanced platelet responsiveness and heightened thrombus formation following arterial injury. Bleeding risk wasn’t significantly elevated with the treatment, the authors reported.
"The approach developed could potentially be used to target other gut microbial pathways,” Hazen said. “We look forward to advancing this novel therapeutic strategy into humans."
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.