Gene Therapy targets sudden cardiac arrest in athletes

A new study reported in the journal Circulation Research has shown that scientists at the University of Utah Health corrected abnormal heart rhythms in mice by restoring healthy levels of a protein that heart cells need to establish connections with one another.

The protein, GJA1-20k, is underproduced in people with the condition. However, it is hoped the study could also have implications for treating dangerous arrhythmias associated with more common conditions, such as those that can develop soon after a heart attack.

While those with arrhythmogenic cardiomyopathy are born with normal hearts, they begin to develop an irregular heartbeat in their 20s or 30s. These arrhythmias can raise the heart rate to dangerous levels and some individuals with the condition experience sudden cardiac arrest during exercise.

Patients diagnosed with arrhythmogenic cardiomyopathy are advised to restrict exercise. They may also benefit from an implantable defibrillator to control their heartbeat.

As the disease progresses, the heart muscle becomes fatty and fibrotic. This prevents the heart from pumping blood efficiently, and eventually, patients need a heart transplant.

Having studied heart tissue from patients with arrhythmogenic cardiomyopathy who underwent transplant, the scientists discovered a problem with a protein called Connexin 43.

In healthy hearts, Connexin 43 forms channels between adjacent cells, facilitating communication. The diseased hearts made normal amounts of Connexin 43, but it wasn’t at the edges of cells where it belonged.

The team determined this was because there wasn’t enough of a trafficking protein called GJA1-20ka, and used low doses of gene therapy to bring the protein back to normal levels.

This, they confirmed, enabled heart muscle cells to transport Connexin 43 to its proper locations and gave the mice a more normal heartbeat.

While the arrhythmia improved, scarring of the mice’s hearts did remain. However, scientists believe arrhythmia and heart scarring can occur independently and that it could be possible to treat abnormal heart rhythms even when the heart is severely scarred.

With the success of the trial involving animals, it is now hoped the therapeutic protein could eventually find a clinical use for humans.

Related: Could a blood test diagnose myocarditis?