Pig hearts repair and grow stronger in gene therapy trial

Gene therapy reversed heart failure and restored normal heart function, in a study on minipigs.

Heart failure is a chronic, irreversible condition, which occurs when the heart cannot effectively pump enough blood to meet the body's needs. Patients with heart failure have low levels of a critical heart protein, cBIN1. Therefore, researchers from the University of Utah used gene therapy to deliver an extra cBIN1 gene into the heart cells of minipigs with heart failure.

'Even though the animals are still facing stress on the heart to induce heart failure, in animals that got the treatment, we saw the recovery of heart function and that the heart also stabilises or shrinks,' said Dr TingTing Hong, associate professor of pharmacology and toxicology at the University of Utah and co-senior author of the study. Dr Hong added, 'We call this reverse remodelling. It's going back to what the normal heart should look like.'

This study, published in NPJ Regenerative Medicine, aimed to increase cBIN1 levels in minipigs with heart failure. cBIN1 is a protein which creates small membrane folds that regulate calcium movement within heart cells, which is essential for coordinated heart contractions. The gene therapy involved injecting the minipigs with a harmless virus containing a copy of the cBIN1 gene. This virus entered the bloodstream, allowing cBIN1 to be delivered directly to the heart cells.

Following gene therapy, the researchers evaluated the minipigs' heart function and structure. The treated hearts pumped blood more effectively, nearing the efficiency of healthy hearts. Additionally, the treated hearts appeared healthier, as they were thicker and less dilated. Notably, the therapy restored the volume of blood pumped per heartbeat to normal levels. Therefore, the treatment halted the progression of heart failure, and also reversed some damage. This suggests the gene therapy helped the heart repair itself and partially regain critical functions.

Untreated minipigs typically die within a few months. However, all four minipigs that received the gene therapy survived for six months, which was the endpoint of the study.

'In the history of heart failure research, we have not seen efficacy like this,' said Professor Robin Shaw, professor of medicine at the University of Utah and co-senior author of this study. Various therapies have been trialled for heart failure in the past, and have shown improvements in heart function by around five to ten percent. However, this cBIN1 gene therapy improved heart function in minipigs by 30 percent. 

The researchers plan to adapt this gene therapy for human use and apply for human clinical trial approval in 2025. This gene therapy will require toxicology testing and compliance with safety standards before advancing to human trials. 

However, the team is encouraged by these results in their minipig model. Dr Hong said, 'When you see large animal data that's really close to human physiology, it makes you think. This human disease, which affects more than six million Americans – maybe this is something we can cure.'