According to the German Heart Foundation, around four million people in Germany suffer from heart failure, also known as cardiac insufficiency. In Europe, estimates suggest that more than 15 million people are affected. Every year, more than 450,000 patients in Germany alone require hospital treatment for heart failure, making it one of the most common causes of hospitalisation. Part of the burden of disease is due to disturbances in the electrical signal transmission in the heart. Implanted pacemakers and so-called cardiac resynchronisation devices, which use targeted electrical impulses to ensure a synchronised heart rhythm, can alleviate the symptoms of many patients, but are not equally effective for all those affected and do not remedy the underlying cellular causes.
An international research consortium now wants to change this: a novel gene therapy is intended to normalise electrical activity in the heart muscle in a targeted and permanent manner. The CONDUCTION-GTx project (Normalising Ventricular Conduction in Heart Failure by Gene Therapies), with a total budget of two million euros, is being funded by four European heart research institutions in Germany, the United Kingdom, France and the Netherlands as part of the International Cardiovascular Research Partnership Awards (ICRPA). The German project funding of 499,925 euros is provided by the German Centre for Cardiovascular Research (DZHK) and goes to the University Medical Centre Göttingen (UMG). There, the project is being led by Prof. Dr. Constanze Schmidt, Director of the Department of Cardiology and Pneumology at UMG, together with Priv.-Doz. Dr. Felix Wiedmann, Senior Physician at the Department of Cardiology and Pneumology at UMG.
In addition to Göttingen, three other research locations are involved: Imperial College London in the United Kingdom, Amsterdam University Medical Centre in the Netherlands and the University of Bordeaux in France. The respective national funding partners are the British Heart Foundation, the Dutch Heart Foundation, the Lefoulon-Delalande Foundation and the DZHK in Germany.
‘Our international research team provides an excellent foundation for advances in the field of translation – the transfer of scientific findings into a new heart therapy,’ says Prof. Schmidt. ‘We are delighted to be able to contribute to the development of new treatment options for many patients with this project.’
Development of new treatment strategies
The aim of the three-year CONDUCTION-GTx project is to develop a new treatment strategy that directly addresses pathological changes in the heart. The researchers are using a specially developed virus that specifically introduces genes into heart muscle cells. These genes produce proteins in the heart muscle cells that are crucial for the transmission of electrical signals, thereby correcting the disturbed electrical activity at the cellular level.
‘With our approach, we want to intervene specifically in the processes at the molecular level and thus achieve a long-term effect. The aim is to treat both the symptoms and the underlying pathological changes in the heart,’ says Dr. Wiedmann.
About the project
The focus is on three central target structures that have been shown to influence stimulus transmission in the heart: (1) sodium channels, which ensure that sodium ions enter the heart muscle cells quickly and that electrical signals are transmitted reliably, (2) gap junctions, connections between neighbouring heart muscle cells that enable the direct exchange of electrical impulses, and (3) transcription factor Tbx5, which regulates the activity of certain genes that are crucial for the development and function of the conduction system. Disruptions in any of these areas can impair electrical signal transmission in the heart and thus worsen heart function. Gene therapy addresses precisely this issue by specifically introducing genes into the heart muscle cells that help to restore or improve the function of the sodium channels, gap junctions and the transcription factor Tbx5. The effect of the therapy will first be tested in preclinical studies in animal models and on human heart tissue. The project is supplemented by computer-assisted simulations designed to calculate the transferability to humans and the optimal administration of the therapy.
Another focus is the comprehensive and Europe-wide unique analysis of the ventricular conduction system in healthy and damaged human hearts. The ventricular conduction system is a specialised system in the heart that is responsible for the coordinated and rapid propagation of electrical impulses in the ventricles. Modern techniques are used, such as spatial transcriptomics, a method for visualising active genes in different areas of the heart tissue, and optical representation of the spread of electrical excitation. The aim is to create a detailed overall picture of the cell structures and processes involved, which will serve as a basis for the further development of future therapies.
The ICRPA funding programme
Since 2018, the International Cardiovascular Research Partnerships Awards (ICRPA) programme has been specifically promoting international collaborations with innovative approaches in cardiovascular research. It places particular emphasis on preclinical research with high clinical relevance and methodological excellence. The current funding round is already the sixth since the programme was launched.
Source: Press release Göttingen University Medical Centre
