New gene therapy appears to reverse effects of heart failure
As of right now, heart failure is irreversible. The chronic condition, in which the heart doesn’t pump blood as well as it should, can be treated with medication and lifestyle changes that slow its progression, but there is no treatment to completely reverse the disease.
The good news is researchers at University of Utah Health have discovered a new gene therapy that has been found to reverse the effects of heart failure and restore heart function in a large animal model.
The therapy can increase the amount of blood the heart is able to pump and drastically improve survival, according to a research paper that describes the results as “an unprecedented recovery of cardiac function.”
The researchers were focused on restoring the heart protein cBIN1, or cardiac bridging integrator 1. The protein is lower in patients with heart failure, and the lower it is, the greater the risk of developing severe disease.
“When cBIN1 is down, we know patients are not going to do well,” said Dr. Robin Shaw, director of the Nora Eccles Harrison Cardiovascular Research and Training Institute at the University of Utah and co-author on the study. “It doesn’t take a rocket scientist to say, ‘What happens when we give it back?'”
In an effort to increase protein levels in heart failure, the researchers turned to a harmless virus commonly used in gene therapy to deliver an extra copy of the cBIN1 to heart cells. The virus was injected into the bloodstream of pigs suffering from heart failure.
As the virus moved through the bloodstream, it delivered the cBIN1 gene into the heart cells. The treatment not only prevented heart failure from worsening but improved some key measures of heart function, suggesting the heart was actually repairing itself.
Shaw said this kind of reversal of existing damage is extremely unusual.
“In the history of heart failure research, we have not seen efficacy like this,” Shaw said. “Previous attempted therapies for heart failure have shown improvements to heart function on the order of 5 to 10%. CBIN gene therapy improved function by 30%. It’s night and day.”
If the gene therapy shows similar results in clinical trials down the road, it could help heal the hearts of the one in four people who will eventually develop heart failure.
Throughout the trial, the animals did experience the same level of cardiovascular stress that led to heart failure. However, the treatment restored the amount of blood pumped per heartbeat back to normal levels.
“Even though the animals are still facing stress on the heart to induce heart failure, in animals that got the treatment, we saw recovery of heart function and that the heart also stabilized or shrinks,” said Dr. TingTing Hong, associate professor and toxicology and CVRTI investigator and co-author of the study at the U of U. “We call this reverse remodeling. It’s going back to what the normal heart should look like.”
The researchers are hoping cBIN1’s role will help cBIN1 gene therapy succeed and introduce a new pattern of heart failure treatment targeting the heart muscle itself.
“CBIN1 serves as a centralized signaling hub, which actually regulates multiple downstream proteins,” said Jing Li, associate instructor at CVRTI and first author of the study. “By organizing the rest of the heart cell, cBIN1 helps restore critical functions of heart cells. CBIN1 is bringing benefits to multiple signaling pathways.”
Along with industry partner TikkunLev Therapeutics, the research team is adapting the therapy for use in humans and plan to apply for approval from the Food and Drug Administration for human clinical trials in the fall of 2025.
“When you see large animal data that’s really close to human physiology, it makes you think,” Hong said. “This human disease, which affects more than 6 million Americans – maybe this is something we can cure.”