The Challenge of Atrial Fibrillation and Heart Failure
Atrial fibrillation (AF) is the most common type of irregular heartbeat, affecting 1-2% of people worldwide. When combined with heart failure (HF), AF worsens outcomes and increases the risk of death. AF tends to get worse over time, and current treatments, especially for those with HF, are limited in both options and effectiveness. Most therapies don’t address the root causes like inflammation and scarring in the heart, leaving a big gap in treatment options.
A New Target: The SK4 Potassium Channel
Recently, we discovered a promising new target for AF treatment: the SK4 potassium channel, which is found in heart muscle cells, fibroblasts, and immune cells called macrophages. This channel becomes more active in patients with AF and in animal models of HF.
We developed a new drug called BA6b9 that blocks this channel in a specific way. In tests on rats with HF, BA6b9 not only reduced the chances of AF starting but also prevented harmful changes in the heart that lead to AF getting worse.
We believe SK4 channels contribute to irregular heart rhythms and inflammation. Blocking these channels in HF patients could help prevent AF from developing and progressing. To explore this, we’ve formed a multidisciplinary team with experts from different fields to study how SK4 channels affect AF and to improve BA6b9.
Key Research Objectives
The project focuses on developing BA6b9, a promising drug that blocks the SK4 potassium channel, which plays a key role in AF progression, especially in HF patients.
- Optimizing BA6b9: Enhance its effectiveness, selectivity, and safety to ensure it targets the SK4 channel without affecting other bodily functions.
- Testing Efficacy: Evaluate its impact in various models, from lab-grown heart cells to animal models like rats and pigs, to determine if it can prevent AF triggered by HF.
- Understanding SK4 Channels: Investigate how SK4 channels influence heart cell behavior using human stem cell-derived heart cells, including those from patients with genetic conditions that increase AF risk.
- Analyzing Human Data: Examine SK4 channel levels in patient data and link findings to clinical outcomes.
Broader Impact and Funding Support
This project, funded by the ERA4Health CardioNNov program, aims to provide new insights into SK4 channels as a treatment target, potentially offering a better way to prevent AF in patients with HF. The ERA4Health CardioNNov program is part of a larger European initiative aimed at advancing innovative therapeutic strategies for cardiovascular diseases. It operates under the Horizon Europe Framework Programme and involves 20 funding organizations from 16 countries, working together to support transnational research projects.
Fostering Collaboration Across Disciplines
The program aims to foster collaboration across disciplines and countries, enhancing research in heart disease prevention, treatment, and management. Its funding emphasizes innovative solutions to significant cardiovascular health challenges, offering support for projects like the SK4 channel research, which could potentially revolutionize atrial fibrillation therapies in heart failure patients.
Prof. Dr. Bernard Attali
Department of Physiology and Pharmacology, Tel Aviv University, Israel
Prof. Dr. Yoram Etzion
Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Israel
Prof. Dr. Bianca Brundel
Department of Physiology, Amsterdam UMC, VUmc, Amsterdam, The Netherlands
Prof. dr. David Filgueiras Rama,
Centro Nacional de Investigaciones Cardiovasculares Carlos III (F.S.P.), Madrid, Spain
Prof. dr. Matteo Mangoni,
Département de Physiologie et Cancer, Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, France
The AFIP foundation
The AFIP foundation will help to the implementation the research findings of the SK4Block-AFHF project by sharing the outcomes with the patient community via our platform.