Genetic heart diseases are caused by defects in the DNA that can cause severe heart failure and / or cardiac arrest. At the moment we are unable to predict if and when patients with genetic heart disease become ill and how serious the disease will become. Recent evidence suggests that metabolic stress can accelerate genetic heart disease. Both stress from the body that acts on the heart as well as stress that arises from the heart muscle cells themselves are thought to contribute. We expect that these two forms of stress add up to determine if and when mutation carriers will develop the disease.
The Dutch Heart Foundation has awarded a grant of 3 million euros to the research consortium DOUBLE-DOSE, which stands for: ”Determinants of susceptibility in inherited cardiomyopathies: towards novel therapeutic approaches”. Rudolf de Boer (UMCG cardiology) and Jolanda van der Velden (Physiology, Amsterdam UMC) are the project leaders of this research. UMCG cardiologist Daan Westenbrink is principal investigator and work package leader at DOUBLE-DOSE. De Boer and Westenbrink are very pleased with this opportunity to improve the lives of patients with genetic heart disease. DOUBLE-DOSE will, among other things, provide a nationwide infrastructure for genetic heart muscle diseases, which is accessible to doctors and researchers, and will also evaluate new treatments.
Over the past 4 years, the DOSIS consortium has found preliminary indications that the cardiomyopathy-causing mutation leads to metabolic stress in the heart muscle cells, and that metabolic stress, such as obesity, accelerates disease progression. The larger DOUBLE-DOSE consortium will test the hypothesis that metabolic stress is key to the pathological mechanism of early and late cardiac dysfunction. To this end, the consortium has been reinforced with scientists with expertise in clinical research in children and adults with dilated cardiomyopathy.
Using clinical data, blood and tissue samples, and experimental models we will determine how metabolic stress and fat accumulation in muscle cells causes cardiac dysfunction in mutation carriers. The researchers will translate the metabolic targets into clinical practice by starting a clinical trial in the early phase of cardiomyopathy.
They will study, among other things, whether obese mutation carriers develop heart muscle disease sooner. In addition, they will perform in dept. molecular studies to investigate how the mutation itself causes harmful changes to heart muscle cells. The knowledge generated by this research will be used to develop new treatments. The research is funded by the Dutch Cardiovascular Alliance and in addition to the experimental cardiology department of the UMCG, the Amsterdam UMC, UMC Groningen, Maastricht UMC, Erasmus MC Rotterdam, Maastricht University, Trimbos Institute and UMC Utrecht are involved in this research.
DOUBLE DOSE is a collaboration between Amsterdam UMC, UMC Groningen, Erasmus MC, UMC Utrecht and Maastricht UMC. Other UMCG’s participating in DOUBLE-DOSE are cardiologist Maarten van den Berg and medical biologist Herman Silljé. Read more about double dose here.