After a heart attack, the heart immediately begins to try to rebuild itself, but that process is seriously hampered by inflammation and scarring. That’s why cardiac functioning declines after a heart attack, and patients are left with permanent damage that significantly increases the risk of future cardiac illnesses like chronic heart failure.
Scientists at Vanderbilt University say they’ve found a potential way to improve the process of cardiac recovery, and it comes from an unlikely source—a compound in Roche’s library that was initially designed to treat rheumatoid arthritis. They showed that the drug, SYN0012, changed how the heart responded to inflammation in mouse models of heart attack, thereby improving cardiac functioning. They reported the results in the journal JCI Insight.
SYN0012 works by blocking the protein cadherin-11, a major culprit in inflammation of heart tissue. In mice, the drug increased the recruitment of cells to the heart that seemed to help rebuild blood vessels. It also limited the activity of fibroblasts, cells that help remodel the heart after a heart attack, so the process didn’t create too much scarring.
“Some amount of inflammation is necessary in myocardial infarction,” said senior author W. David Merryman, Ph.D., professor of biomedical engineering, pharmacology, medicine and pediatrics at Vanderbilt, in a statement. Inhibiting cadherin-11 could allow “more precise control over the amount of inflammation in the fibrotic remodeling process,” he added.
Roche Innovation Center in Basel supplied the SYN0012 for the Vanderbilt study. Roche had been interested in targeting cadherin-11 in rheumatoid arthritis, but it pulled back from that research effort last year as part of a routine culling of its pipeline.
SYN0012 isn’t the only drug researchers have suggested could be repurposed in heart disease. In May, scientists at the University of Manchester published a study showing that Eli Lilly’s blockbuster PDE5 inhibitor to treat erectile dysfunction, Cialis, effectively treated heart failure in sheep models. It wasn’t entirely surprising, considering that PDE5 inhibitors were originally studied in heart disease.
A team at Imperial College London is investigating the potential of treating heart disease by targeting the protein MAP4K4, and researchers at Baylor College of Medicine have investigated inhibiting the Hippo signaling pathway to improve the ability of heart muscle to repair itself.
The goal of the Vanderbilt team is not to stop inflammation altogether after a heart attack, but to fine-tune it. “Importantly, targeting [cadherin-11] with SYN0012 in mice does not prevent the acute inflammatory and reparative response, but rather it selectively acts on several cell populations to reduce the duration of inflammation and the extent of fibrotic remodeling,” Merryman and colleagues wrote in the study.