Jump to content
Powered by

Genetic causes and therapy of cardiac insufficiency

The Department of Cardiology at the University Hospital in Heidelberg coordinates the Germany-wide Cardiovascular Network in the National Genome Research Network (NGFN). The Cardiovascular Network is investigating the genetic causes of cardiovascular diseases. In the follow-up programmes "NGFN-plus" and "NGFN-transfer", new research projects dealing with cardiac insufficiency will now be funded with more than €11 million.

Since 2001, the Medical University Hospital in Heidelberg has coordinated the Cardiovascular Network within the framework of the National Genome Research Network (NGFN), which also involves nine other big German university hospitals. The Cardiovascular Network’s spokesperson is Prof. Dr. Hugo Katus, Medical Director of the Dept. of Internal Medicine III / Cardiology, Angiology and Pulmonlogy at the University Hospital in Heidelberg; Dr. Tanja Weis is coordinating the network activities.

The treatment of cardiac insufficiency with cell therapy is still a long way off

The network’s research focuses on clarifying the genetic causes and development mechanisms of cardiovascular diseases, which are by far the most frequent causes of death in industrialized western countries. This task can only be mastered if clinicians and basic researchers work closely together in interdisciplinary research approaches, as Katus explains.
Prof. Dr. Hugo Katus, Medical Director of the Dept. of Cardiology at Heidelberg University Hospital (Photo: University Hospital Heidelberg)
Genetic population research focuses on identifying genes related to cardiovascular diseases. The function of these genes is then analysed in animal models. Future therapeutic approaches might involve the molecular repair of such genes. According to Katus, the possibility of transforming stem cells into what are known as pacemaker cells that could be implanted in patients suffering from cardiac insufficiency or arrhythmias rather than using an artificial pacemaker is an interesting research perspective, but still far into the future.

As NGFN funding comes to an end in May 2008, the BMBF launched the two follow-up programmes “NGFN-plus” and “NGFN-transfer”, which are intended to give medical genome research in Germany a new orientation. The focus is on translational medicine, i.e. the direct transfer of laboratory bench results into clinical diagnostics and therapy for the benefit of patients.

”NGFN-plus“ and “NGFN-transfer“

The Department of Cardiology at Heidelberg University is involved in both funding programmes with several big projects on the topic of cardiac insufficiency. Under the “NGFN-plus” programme, Heidelberg once again coordinates a new Germany-wide network dealing with the investigation of the genetic causes of cardiac insufficiency.
Computer heart model (Photo: Prof. Denis Noble, Oxford University, UK)
“We are now able to carry out multicentre studies with more than 1,000 patients suffering from all kinds of myocardial diseases, for example left-ventricular hypertrophy or atrial fibrillation,” explained Katus when it became known that the network was to be funded with €9 million from the BMBF. The studies will investigate the genome of patients for differences that might be responsible for or trigger the observed defects. The researchers are specifically looking for sequence alterations of genes that are homologous to those associated with cardiac diseases in the animal model.

The Department of Bioinformatics at the German Cancer Research Centre and the Department of Genetic Epidemiology at the Leibniz Institute for Arteriosclerosis Research in Münster are working on the development of the computer programmes required as well as the processing of the huge quantities of data arising from the investigations. Other partners in the “Cardiac Insufficiency” network include the university hospitals in Göttingen and Munich as well as the Charité Hospital and the Max-Delbrück Centre for Molecular Medicine in Berlin.

Zebrafish as model

Zebrafish in the aquarium (Photo: University Hospital Heidelberg)
One of the most popular animal models for cardiovascular diseases are zebrafish which are the major focus of a group of researchers led by Dr. Wolfgang Rottbauer in the Department of Cardiology. The larvae are transparent, which makes it possible to investigate abnormal processes on the heart of the living animal under a light microscope. The larvae develop very quickly and their heart corresponds to the heart of a newborn mammal after 72 hours.

Zebrafish embryo with heart (Photo: University Hospital Heidelberg)
Another advantage is that the fish larvae are able to survive the first ten days of their development without a functional heart. This enables the investigation of diseases that might be absolutely fatal in other organisms.

Rottbauer’s team has identified a number of zebrafish genes whose defects lead to cardiac insufficiency. One of these genes is the “dead-beat” gene which affects the signaling pathway of the vascular endothelial growth factor (VEGF). VEGF is a growth factor that regulates the generation and permeability of blood vessels. If a gene mutation switches off the VEGF signaling pathway, this triggers severe cardiac insufficiency since the heart chambers are no longer able to properly retract and subsequently lose their pumping power. Another mutant (msq) is characterized by the defective function of the integrin-linked kinase (ILK). ILK works like a mechanical sensor that senses the stretching of the myocardial cells when under greater physical strain than normal. The msg mutation in the ilk gene prevents heart cells from perceiving changes in blood pressure or heart filling. As a result, the heartbeat of the fish becomes weaker and finally the heart stops.

Innovation transfer

The “NGFN-transfer” funding programme funds projects that are directly transferred into medical practice in cooperation with research-based companies. With a purse of €1.2 million, the BMBF is funding the collaborative project of Dr. Norbert Frey’s team and the Berlin-based biotech company “Metanomics”. The project is seeking to compare metabolic products of diseased and healthy myocardial cells. “This provides us with information on the processes that are affected in the different forms of cardiac insufficiency and means that we are able to develop an individualized therapy with drugs that are best suited to the specific kind of cardiac insufficiency,” explains Frey, lecturer and chief physician in the Department of Cardiology at Heidelberg University.
Prof. Dr. Markus Hecker (Photo: University of Heidelberg)

Under the “NGFN-transfer” programme, €1.1 million are given to a project dealing with the therapy of cardiac insufficiency coordinated by Prof. Dr. Markus Hecker, Director of the Institute of Physiology and Pathophysiology at the University of Heidelberg. This work is being done in cooperation with the biotech company Avontec GmbH in Martinsried. Hecker, who was also involved in establishing the company, and Avontec are developing medications on the basis of nucleic acids that are able to switch off specific genes that are responsible for cardiac insufficiencies, and hence restore the normal function of cardiac cells. Avontec was established in 2001 by Hecker and Prof. Dr. Gerd Hasenfuß in Göttingen. In 2003, Hecker received the German Start-Up Award for their excellent concept.

EJ – 15.01.2008
© BIOPRO Baden-Württemberg GmbH

Further information:
Dr. Ernst-Dieter Jarasch
BioRegion Rhein-Neckar-Dreieck e.V.
Im Neuenheimer Feld 582
69120 Heidelberg
Tel.: +49 (0)6221-64 922 0
Fax: +49 (0)6221-64 922 15
E-mail: jarasch(at)bioregion-rnd.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/genetic-causes-and-therapy-of-cardiac-insufficiency