Heart failure affects just over 64 million people worldwide and between 400,000 and 700,000 people in France. (see box below). Despite the number of people affected and the high mortality rate caused by this disease, there are few therapeutic options for patients. In fact, the choices are generally limited to a change in the patient's lifestyle, through diet or stopping the consumption of toxic products such as alcohol, an operation, the installation of a ventricular assist device (VAD) to help the heart pump blood, or even a heart transplant. Thus, the options for combating the disease and prolonging life expectancy are quite limited: on average, 81.3% of patients die within a year of their diagnosis.
However, researchers from the University of Utah Health (USA) have looked into solutions that can be provided to patients suffering from heart failure. Thus, the scientists carried out their experiments on pigs, because their hearts have a physiology quite close to that of humans. The results of this study were published in the journal Nature.
What is heart failure?
L'heart failure is a heart disease that renders the heart muscle incapable of normally ensuring the propulsion of blood throughout the body, meaning that the heart's ability to pump blood to meet the body's needs is greatly diminished. According to the Montreal Heart Institute (Canada), the causes of heart failure can be multiple: from heart malformations to heart disease to excessive alcohol consumption, many factors can play a role in the development of this heart disease. According to the French Society of Cardiology, heart failure affects between 1 and 2% of the general population, with an increase in risk as we age.
During their research, the team of specialists realized that when an individual suffers from heart failure, a protein in heart cells decreases in quantity. This observation was also made in mice and pigs. This protein is cardiac bridging integrator 1 (abbreviated cBIN1). "When cBIN1 levels are low, we know patients are not going to do well," "The study was co-authored by Dr. Robin Shaw, a heart specialist at the University of Utah. So he asked himself the following question: what happens to patients who have this protein reinjected into their heart cells?
"We have never seen such efficiency"
To answer this question, this scientist and his team decided to use pigs by making them undergo, via stimulations of a pacemaker, very high heartbeats, around 170 beats per minute, so that they develop heart failure. They were then able to inject directly into the blood vessels of the animals the protein cBIN1, contained in an adeno-associated virus (i.e. a small virus containing genes and already existing in humans and pigs). The protein, passing through the blood vessels of the animal, via the virus, was then able to go directly into the heart cells of the pigs.
Read also Heart shape may influence risk of cardiovascular disease
The pigs that underwent this gene therapy (see box below) remained under the same stress conditions throughout the study, meaning that for six months, their heartbeats remained elevated by stimulation. However, according to the scientists, the four pigs that received these injections remained alive until the end of the study, instead of dying within a month if they had not received it. In addition, the treatment not only prevented their situation from getting worse, it even improved it! In fact, the heart even began to repair itself, meaning that some of its functions improved. "We have never seen such efficacy in the entire history of heart failure research," rejoices Dr. Robin Shaw.
Indeed, several previous attempts at treatments studied to combat heart failure have shown signs of improvement in heart function only from 5 to 10%. However, gene therapy based on cBIN1 has shown signs of improvement in heart function up to 30%. Heart function is restored, including improved blood pumping, reduced blood pressure and sometimes even a reduction in the size of the heart, which could go as far as returning to a shape almost similar to that of a healthy heart. According to Dr. Shaw, "it's day and night", between these treatments and their results.
What is gene therapy?
There gene therapy is a therapeutic strategy aimed at modifying the genes present in certain cells in order to cure a disease. Gene therapies are already used, in particular to combat certain rare diseases. As for gene therapies targeting the heart, they seek to stimulate the formation of new blood vessels. Many researches and studies are underway in order to be able to find one that can be effective against heart failure.
Gene therapy to be tested on humans in fall 2025
Scientists are therefore hopeful that this gene therapy could be applied to humans in the near future. "When you see data like this on large animals with physiology close to that of humans, it makes you think and you say to yourself that maybe you can cure this disease.", enthuses TingTing Hong, co-author of the study.
Read also Cardiovascular diseases kill 10,000 people a day in Europe: salt to blame
The team of researchers therefore plans to apply for authorization to test this therapy on humans, as early as the fall of 2025, from the FDA (or Food and Drug Administration), the American administration responsible for monitoring food and drug products. However, this gene therapy must still pass numerous tests and toxicological studies to ensure its safety for humans. In addition, as with most gene therapies, it remains to be seen whether it will work in people who have acquired natural immunity against the adeno-associated virus carrying the cBIN1 protein.
English 
French