·  Legal News, Analysis, & Commentary

Health & Medicine

Gene Therapy Make be the Cure for Sudden Cardiac Arrest in Athletes

— April 5, 2023

Scientists discover a new revolutionary treatment for addressing abnormal heart rhythms and sudden death.

University of Utah Health scientists have corrected abnormal heart patterns in mice by restoring healthy levels of a specific protein called GJA1-20k that heart cells need to form connections with each other. This protein is underproduced in people with a condition called arrhythmogenic cardiomyopathy, one of the leading causes of sudden cardiac arrest in athletes under the age of 35. The findings offer a new strategy for treating arrhythmogenic cardiomyopathy and might lead to solving the riddle to dangerous arrhythmias associated with more common conditions, such as those that can develop soon after having a heart attack.

Arrhythmogenic cardiomyopathy is genetic and has the possibility of being passed down through generations. In this process, healthy heart muscle (myocardium) is replaced by both scar tissue (fibrosis) and fat which affects the right ventricle, the left ventricle, or both ventricles. Individuals who suffer from arrhythmogenic cardiomyopathy are born with normal hearts but begin to show signs of the condition in their twenties or thirties. This, they may have no problem exercising for years, then one day, be forced to slow down or stop altogether. If they don’t, they could face sudden death.

Arrhythmias can raise the heart rate to life endangering heights and cause individuals with the condition to sometimes experience sudden cardiac arrest during exercise. If diagnosed with arrhythmogenic cardiomyopathy, most doctors recommend restricting exercise. Some people also benefit from an implantable defibrillator to control their heartbeat. 

Gene Therapy Make be the Cure for Sudden Cardiac Arrest in Athletes
Photo by Andrea Piacquadio from Pexels

Due to having this particular condition, the heart muscle becomes fatty and fibrotic, preventing it from pumping efficiently. Eventually, patients generally require transplant surgery.

The study was done on heart tissue from patients with arrhythmogenic cardiomyopathy who underwent transplant surgery. The results revealed a problem with a protein called Connexin 43. This protein forms channels between adjacent cells, facilitating communication. Unhealthy hearts showed unusual behavior as the Connexin 43 wasn’t located properly at the edge of the cells where it belongs. The team theorized that it was likely because there wasn’t enough of a trafficking protein called GJA1-20K. The researchers already knew from prior experimentation that without it the heart’s cells wouldn’t be able to get Connexin 43 to the designated location.

Scientists turned to their group of mice which had similar heart palpitations and irregular beating. With gene therapy testing that was completed, they confirmed GJA1-20k was back up to normal levels, and enabled heart muscle cells to transport Connexin-43 to its proper location. Also, it was found there was heart scarring from another condition in the mice, and because these mice were treatable for arrhythmogenic cardiomyopathy, this led to a new paradigm suggesting that arrhythmia and heart scarring can occur independently.

Scientists should now be able to further respond and treat abnormal heart rhythms even when the heart is severely scarred. They believe the results of raising levels of GJA1-20k in mice is transferrable to humans. Another possible outcome is the potential for a direct injection of the protein into the heart itself that can successfully treat arrhythmogenic cardiomyopathy. 

Because the findings showed disruption in protein traffic is thought to contribute to arrhythmias beyond those of arrhythmogenic cardiomyopathy, similar treatment strategies might be useful for those conditions as well. Hopefully one day soon, the need for ion channel-blocking drugs, which can slow the heart and lead to new heart rhythm issues, will be replaced by more effective interventions.


Translation of New and Emerging Therapies for Genetic Cardiomyopathies

Gene therapy to treat cardiac arrhythmias

New Gene Therapy Targets Cause of Sudden Cardiac Arrest in Athletes

Join the conversation!