– SK4BLOCK-AFHF

Atrial fibrillation (AF) is a prevalent heart rhythm disturbance (arrhythmia) affecting the upper chambers of the heart (atria). Heart failure (HF) is a severe medical condition associated with pumping dysfunction of the lower heart chambers of the heart (ventricles). AF and HF are two medical problems often coexisting in the same patient and leading to poor clinical outcome. AF itself is affecting worldwide approximately 33.5 million individuals and is associated with severe complications and increased mortality. AF has a progressive nature associated with various changes in the atria leading to recurrence and persistence of the arrhythmia. Existing therapies are limited especially in HF patients and do not target the atria changes leaving substantial unmet need for therapeutic innovation. We revealed that a protein called SK4 calcium-activated K+ channel (SK4 channel), is upregulated in atria of rats that suffer from HF. Moreover, we succeeded to design a novel compound called BA6b9 that block the function of SK4 channels and can reduce AF as well as detrimental atrial changes in rats with HF. Here, we raised a multidisciplinary consortium, whose partners will work in synergy and with complementary expertise to: comprehensively explore the role and mechanisms of SK4 channels in AF progression; design optimized BA6b9-derived molecules to further test their effectiveness and safety in various AF models; examine SK4 channel expression and localization in human atrial tissue samples. Overall, our new target approach will provide us with a unique and personalized therapeutic strategy to inhibit AF burden in HF patients.