More than half a million Americans are diagnosed with heart failure every year – a disease that is incurable without a heart transplant. Now researchers at Temple University School of Medicine (TUSM) in Philadelphia have discovered a commonly prescribed antidepressant has the ability to reverse heart failure.
The study was based on two decades of research on the enzyme GRK2, led by Dr. Walter Koch, director of the Center for Translational Medicine at TUSM. Findings showed levels of GRK2 rise when the heart is failing. When the enzyme level was decreased, heart failure reversed. Scientists then linked the findings to data proving that the common antidepressant paroxetine, commonly known as Paxil, has a side effect that allows it to inhibit GRK2, therefore restoring heart function in mice.
When the heart muscle is damaged by a heart attack, the body attempts to compensate for its lost pumping power, ultimately leading to a larger, less efficient heart. GRK2 plays a major role in this process, which leaves the heart less able to supply blood to the entire body.
The disease reversal occurred at concentrations of paroxetine similar to those found in the blood of patients treated for depression. It is the first small molecule shown to successfully and selectively turn off GRK2's enzymatic activity, and is already known to be safe in humans. Koch said he hopes next year to begin clinical trials of a gene therapy approach to lowering GRK2 levels. Collaborator Dr. John Tesmer at the University of Michigan is working to create a derivative of paroxetine that is effective in lower doses without the antidepressant effect.
According to the American Heart Association, 5.1 million people live with heart failure. That number is expected to increase 25 percent by 2030. While treatment for the condition has improved in recent years, once the deterioration of the heart muscle begins, there has been no way to reverse it without having a heart transplant. Approximately half of those diagnosed with heart failure die within five years.
Koch's team tested paroxetine against a placebo and another antidepressant, fluoxetine, commonly known as Prozac. Mice with induced heart failure were treated with placebo, paroxetine, or fluoxetine. Only paroxetine-treated mice showed restored heart function.
Traditionally, drugs for heart failure must be taken for life, but in the paroxetine study, the improvement was maintained when the mice were treated for four weeks and then left untreated for two.
"We think we reset the system. We stopped the vicious cycle of heart failure and restored basic function," Dr. Sarah Schumacher, lead author of the study said in a news release.
“We saw active reversal of ventricular function, reverse remodeling, heart chambers actually got smaller and more muscular, and stoppage of fibrosis that limits the stiffness of the heart,” Koch told FoxNews.com. “In addition, several molecular and genetic biomarkers that are characteristic of the failing heart were reversed by paroxetine.”
The findings were published in the March 4 issue of the journal Science Translational Medicine.
Koch said the research results could mean a totally new class of drugs for heart failure.
“GRK2 inhibitors would offer hope for millions of people if they can be successfully developed,” he said