About the project
This project has received governmental financial support via Innovation Fund Denmark and was initiated in 2014.
Target-AF is private-public collaboration between the Danish biotech company Acesion Pharma and the Ion Channel Group, University of Copenhagen. By joining forces and utilizing our expertise’s we aim at discovering and developing new and safe antiarrhythmic drugs for treatment of patients with atrial fibrillation.
Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is caused by irregular electrical activity in the heart upper chambers (atria) which causes them to contract irregularly (fibrillate). As blood is not pumped correctly, it pools in the atria.
AF is associated with impaired quality of life, increased rate of hospitalisation, and increased risk of stroke and death. AF affects 1-2% of the total population in the EU, and the lifetime risk for developing AF is 25% for individuals over 40 years of age underscoring the important public health burden posed by AF.
Current pharmacological treatment of AF is characterised by drugs with low efficacy or adverse effects. Hence, there is a great medical need for new safe and effective treatments for AF.
Our goal is to discover and develop new and safe treatments for atrial fibrillation.
The main molecular focus of the project is ion channels. Ion channels are membrane proteins that facilitate the movement of ions across cell membranes. The coordinated contraction of the heart is governed by an electrical impulse that spreads throughout the cardiac muscle. This electrical signal is generated by the coordinated opening and closing of ion channels.
“Target-AF” consists of two projects focusing on ion channels:
Novel atrial selective ion channel targets for treating AF
Different ion channels are expressed in different parts of the heart. By targeting ion channel primarily expressed in the atria of the heart ventricular adverse effects might be avoided. The project therefore aims at identifying and validating new atrial selective ion channel targets and investigating their potential as drug targets for treating AF. This is achieved by using a number of techniques including in vitro and in vivo electrophysiology, isolated heart preparations and sophisticated models of AF.
Role of ion channels in fibroblast and cardiac fibrosis
Over time, AF patients become refractory to anti-arrhythmic treatment, meaning that the drugs are no longer effective. Partly, this is caused by increased atrial fibrosis as the disease progresses. Finding ways to limit the progression would be a major achievement in AF therapy. Cardiac fibroblasts and myofibroblasts are the main producers of extracellular matrix (ECM) proteins. Under physiological conditions this is important for organizing the cardiac cellular structure. In atrial fibrillation, the cardiac fibroblast produce increased quantities of ECM proteins leading to tissue fibrosis. This structural remodeling of the heart impairs electrical and mechanical function and creates a substrate for arrhythmia.
We are seeking to understand the role of fibroblast ion channels in cardiac fibrosis and to investigate the therapeutic potential of pharmacological modulation of these.
Bo Hjorth Bentzen