A team led by researchers at Temple University School of Medicine (TUSM) found that a commonly prescribed antidepressant restored heart function in mice with heart failure, a finding that could lead to clinical trials for a disease long considered irreversible.
The team, which was led by Walter J. Koch, PhD, the William Wikoff Smith Endowed Chair in Cardiovascular Medicine and Director of the Center for Translational Medicine at TUSM, found that the antidepressant paroxetine (also known as Paxil), reversed heart failure in mice. The findings were published in the journal Science Translational Medicine. The effect of paroxetine was not because of its antidepressant properties, but the inhibition of a specific enzyme that is a side-effect of the drug.
“This may open the way for a new class of therapies for a disease for which we lack effective interventions,” Koch said. “At a minimum, the research suggests that physicians may want to consider prescribing paroxetine for heart failure patients who also suffer from clinical depression. If you have to give these patients an antidepressant, why not give them this one, which may improve heart function?” Koch asked.
The disease reversal occurred at concentrations of paroxetine similar to those found in the blood of people treated for depression, although Koch cautioned that what happens in mice is no guarantee of the same response in humans.
More than a half million Americans are diagnosed with heart failure every year, and 5.1 million live with the disease. That number is projected to increase 25 percent by 2030, according to the American Heart Association. The cost of treating the disease will more than double, from $30.7 billion in 2012 to nearly $70 billion in 2030. While treatment has improved significantly in recent years with the use of beta blockers and angiotensin-converting enzyme inhibitors, once the deterioration of the heart muscle begins, there has been no way to reverse it without having a heart transplant. About half the people diagnosed with heart failure die within five years.
The current study grows out of Koch’s two decades of investigation into an enzyme called GRK2, which stands for G protein-coupled receptor kinase-2. Levels of this enzyme rise when the heart is failing. Previous research by Koch and his colleagues has demonstrated the role of GRK2 in heart failure. That research relied on genetic manipulation to control GRK2 levels and, when GRK2 is lowered in various animal models, heart failure is reversed. Koch said he hopes next year to begin clinical trials of a gene therapy approach to lowering GRK2 levels.
In addition to Drs. Koch, Schumacher and Tesmer, the research team included Drs. Arthur M. Feldman, Erhe Gao, Weizhong Zhu, Xiongwen Chen and J. Kurt Chuprun from TUSM.
This work was supported by a Brody Family Medical Trust Fund Fellowship and NIH grants HL086865, R37 HL061690, P01 HL08806, P01 HL075443 and P01 HK091799.