Heart Rhythm 2026

This study explored a new way to prevent atrial fibrillation (AF) by targeting a natural signaling system in the heart. We focused on a protein pathway called NRG1/ERBB4, which is known to support heart development and repair. We tested a drug-like compound called JK07, designed to selectively activate this pathway, in several models: minipigs with high blood pressure–related heart changes, mice with obesity, and human heart cells grown in the lab (which is where I participated myself). Across these experiments, we triggered AF using electrical stimulation to see whether JK07 could reduce the likelihood or severity of abnormal heart rhythms.

The results showed that activating ERBB4 with JK07 significantly reduced the occurrence and duration of AF in both animal models. In minipigs, the treatment also reduced harmful structural changes in the heart, and especially fibrosis, a type of scarring that disrupts normal electrical signaling. Interestingly, in obese mice (which had little or no fibrosis), JK07 still lowered AF risk. This suggested that the drug works not only by improving heart structure but also by directly stabilizing the electrical behavior of heart muscle cells. Supporting this, experiments in human heart cells showed that JK07 could completely prevent abnormal electrical circuits (a key cause of AF) without interfering with normal heart cell function.

These findings are important because current AF treatments often do not address the underlying disease processes in the heart and can have limited effectiveness. By contrast, ERBB4 activation appears to tackle both structural damage and cellular dysfunction, which are two major drivers of AF. This dual action makes it a promising new therapeutic approach. Since JK07 has already shown a good safety profile in early clinical studies for heart failure, it may offer a new pathway toward more effective and targeted treatments for AF in the future.