In what may represent a new frontier in treating one of the world’s deadliest chronic conditions, researchers have developed a gene therapy that appears to reverse heart failure—restoring the heart’s pumping power and dramatically improving survival rates, at least in a large animal model. According to findings published in the journal npj Regenerative Medicine, this novel approach isn’t just slowing the disease—it’s triggering what the study’s authors describe as “an unprecedented recovery of cardiac function.”

If this breakthrough holds up in human trials, it could change the way clinicians think about a disease that affects millions in the U.S. alone. Right now, heart failure—defined by a heart that can no longer pump efficiently—is functionally irreversible. Treatment typically involves managing symptoms, reducing stress on the heart, and waiting for inevitable decline. Eventually, most patients face dire outcomes unless they qualify for a transplant. The notion that simply restoring a single protein to healthy levels could reverse this vicious cycle is as stunning as it is tantalizing.

A Radical Reset for a Failing Heart

The new therapy zeroes in on a key protein called cardiac bridging integrator 1 (cBIN1). Researchers had previously observed that low levels of cBIN1 correlated with worsening outcomes for heart failure patients. “When cBIN1 is down, we know patients are not going to do well,” says Robin Shaw, MD, PhD, director of the Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI) at the University of Utah and co-senior author of the study. “It doesn’t take a rocket scientist to say, ‘What happens when we give it back?’”

To find out, the team used a harmless, gene-delivering virus to ferry extra copies of cBIN1 into the hearts of pigs suffering from heart failure. The results were striking. Not only did every treated animal survive the six-month study period, but the hearts also began to recover their structural integrity and ability to pump blood efficiently. For a disease that can send patients into a downward spiral with few chances of genuine reversal, the improve

ment—on the order of a 30% bump in heart function—“is night and day,” says Shaw.

Critically, the treatment didn’t just hold the line against the disease. In measures that matter most, the hearts actually improved. Blood-pumping ability, a key indicator of heart health, climbed upward, heading toward a near-normal range. Damaged cardiac tissue shrank and thickened, starting to look more like it did before heart failure took hold. This kind of reversion to a healthier state—what researchers call “reverse remodeling”—is essentially unheard of in this line of work.

Even though the pigs continued to face the same underlying stressors that initially drove them toward heart failure, their hearts, newly fortified with cBIN1, seemed equipped to heal rather than degrade. “We call this reverse remodeling,” says TingTing Hong, MD, PhD, associate professor of pharmacology and toxicology at the University of Utah and a co-senior author. “It’s going back to what the normal heart should look like.”

A Master Regulator in the Heart’s Machinery

So, how does restoring a single protein deliver such a sweeping cure? The researchers believe cBIN1 functions as a kind of cellular hub, orchestrating a network of other essential proteins that give heart muscle cells their strength and coordination. “cBIN1 serves as a centralized signaling hub, which actually regulates multiple downstream proteins,” says Jing Li, PhD, associate instructor at CVRTI.

By reinstating this keystone protein, the therapy appears to bring order back to the intricately arranged architecture of the heart’s cells, ensuring these cells can beat in sync and pump blood more efficiently. In essence, cBIN1 is helping re-establish the heart’s internal command center.

With the help of their industry partner, TikkunLev Therapeutics, the research team now aims to adapt the therapy for human use, with hopes of initiating human clinical trials by late 2025. Of course, many hurdles remain. The method will have to undergo toxicology testing and regulatory scrutiny and must contend with the reality that some people’s immune systems might already recognize and neutralize the virus used to deliver the gene. Still, the very existence of large-animal data showing this level of reversal in cardiac damage is almost unheard of.

“When you see large animal data that’s really close to human physiology, it makes you think,” Hong says. For a condition that will eventually affect about one in four people alive today, it’s impossible not to imagine the implications—treatments that not only help a weakened heart eke out a little more life but also help it bounce back. “This human disease, which affects more than six million Americans—maybe this is something we can cure.”