Drug repurposing is one of the fastest and most effective routes to new medical treatments. Researchers reveal how such a strategy may yield a new treatment for heart failure.
First study author Nathan Robbins — from the University of Cincinnati College of Medicine in Ohio — and colleagues recently reported their findings in the Journal of the American Heart Association.
Heart failure is a condition that arises when the heart is unable to pump oxygen-rich blood well enough to support other organs.
It is estimated that heart failure affects around 5.7 million adults in the United States, and around 50 percent of people who have the condition die within 5 years of being diagnosed.
Though there is no cure for heart failure, treatments exist that help to manage the condition. Some of these treatments, such as a left ventricular assist device (LVAD), concentrate on improving the heart's function.
An LVAD is a battery-powered device surgically implanted into the patient's heart. It draws in blood from the left ventricle of the heart, before transporting it to the aorta, or the artery that distributes blood to the rest of the body.
In their new study, Robbins and team reveal how probenecid may offer a noninvasive alternative to such treatments, after finding that the gout drug improved the heart-pumping action of people with heart failure.
'From bench to bedside'
The researchers tested probenecid on 20 people of an average age of 57 years, all of whom had heart failure.
As part of the double-blind, randomized, placebo-controlled study, all the participants either took probenecid or a placebo over 4-week periods between June 2013 and April 2015.
Subjects' ejection fraction, or the heart's ability to pump blood, was measured by echocardiogram. Other measures of heart function included an electrocardiogram and a 6-minute walk test.
Compared with the placebo, the researchers found that probenecid led to improvements in ejection fraction.
"This is the first time," states Robbins, "probenecid has been used in heart failure patients and we showed it increases the ejection fraction in patients with heart failure. It was exciting to be able to see this medicine work from the bench to the bedside."
"We were quite happily surprised it improved the two main ways in how the heart functions," adds study co-author Dr. Jack Rubinstein, of the Department of Internal Medicine at the University of Cincinnati. "It improves how the heart contracts and how it relaxes."
Importantly, the drug was found to cause no significant adverse effects in the subjects. "We know that it was very likely to be safe because the medicine had been taken by people of all ages for decades," says Dr. Rubinstein. "It has a very strong safety profile."
'A new way of treating heart failure'
When the researchers tested the drug on heart cells taken from mice, they found that it improves the heart's use of calcium, which is a key player in heart muscle contraction.
While larger clinical trials are needed to determine the efficacy of probenecid for heart failure, the researchers believe that their results show promise.
"The repercussions are potentially significant — if we are able to confirm this experiment in larger studies with longer-term follow-up, this could present a new way of treating heart failure for which there are limited medical therapies available."
Dr. Jack Rubinstein
"Left ventricular assist devices, pacemakers, heart transplants, and medications are available to treat heart failure patients, but outcomes for patients with heart failure are still worse than outcomes for the vast majority of cancer patients," Dr. Rubinstein adds.
"That's what we want to effectively change."