Key Protein Offers Potential New Treatment for Systolic Heart Failure

However, when it becomes weakened, it can result in severe complications, ranging from debilitating shortness of breath and swelling in the legs and feet to fluid accumulation in the lungs and potentially death. In systolic heart failure, which impacts over 32 million people worldwide, the heart muscle loses its ability to contract forcefully enough to propel oxygenated blood from the left ventricle through the circulatory system. The current treatments employed by cardiologists primarily manage the symptoms of systolic heart failure and are vital for enhancing patients’ quality of life. Nonetheless, these therapies do not directly target the root issue—the weakened heart muscle itself. Researchers have now discovered a protein that has the potential to address this problem.

For the first time, scientists at Fralin Biomedical Research Institute (Roanoke, VA, USAu) have shown that a protein called PERM1 effectively regulates both energy levels and the heart’s contraction capability. The study, published in the American Journal of Physiology, suggests that this protein may offer a novel therapeutic strategy for treating systolic heart failure. In recent decades, various drugs have been developed to enhance heart muscle contraction. However, many of these medications have encountered difficulties in significantly improving long-term health, and most have not succeeded in increasing survival rates in clinical trials. These drugs were designed to either amplify the force of the heart’s contractions or enhance the efficiency of muscle fiber contractions, but both approaches tend to increase energy usage, which can ultimately lead to worse patient outcomes.

The study's findings indicate that the PERM1 protein plays a role in regulating both aspects of this detrimental cycle. Found in both heart and skeletal muscles, PERM1 is known to influence mitochondrial function. Given its presence in contracting muscles, the research team posited that the protein might also impact muscle contraction itself. In their study, the researchers introduced the protein into the hearts of healthy mice using a modified virus known as adenovirus. Viruses serve as effective delivery vehicles because they are adept at navigating difficult areas within the body. The study revealed that the protein not only regulated mitochondrial function, as previously established, but also enhanced the heart’s contraction ability. Conducted in healthy hearts, the next step in the research is to determine whether the protein yields similar effects in hearts that are failing.

“Now we are applying this method in failing hearts to see if delivering PERM1 via adeno-associated virus — a method commonly used for gene therapy — is able to bring back cardiac function and mitochondrial function,” said Junco Warren, a cardiovascular scientist in the Center for Vascular and Heart Research at the Fralin Biomedical Research Institute. “That would further suggest that it may be a new therapeutic to treat systolic heart failure by simultaneously addressing the weakness in the muscle and energy production by the mitochondria.”