8 million for research into heart disease
Transatlantic research project ‘Sarc-Attack’ led from Dortmund investigates the causes of heart disease
The American Leducq Foundation is supporting Stefan Raunser’s heart muscle research at the Max Planck Institute of Molecular Physiology with 8 million euros. Under his leadership, a team of European colleagues from King's College London and the Institut Curie in Paris, together with American clinicians, will investigate the molecular causes of heart disease and the action of novel drugs – with the ultimate goal of improving therapy for patients.
Cardiomyopathies lead to a weakening of the heart muscle and are among the most common causes of morbidity and mortality worldwide. Their hypertrophic (HCM) and dilated (DCM) forms are genetically determined: in HCM the heart‑muscle walls thicken, whereas in DCM they become thinned and floppy. Both extremes impair the heart's pumping ability and give rise to a range of symptoms: persistent fatigue, swollen legs, shortness of breath, chest pain and, occasional fainting spells. Complications can include cardiac arrhythmia, heart failure and, in severe cases, sudden cardiac death.
Research consortium with a comprehensive toolbox
“The heart muscle is the central engine of the human body. Of course, it is easier to fix a broken engine if you know how it is built and how it functions”, says Raunser. “Our team of structural biologists and cardiologists brings together highly complementary expertise and a comprehensive toolbox to find out exactly that.”
To this end, the team wants to investigate how mutations in certain heart muscle proteins impair muscle function. These mutations are responsible for approximately 40-50% of HCM and at least 10-20% of familial DCM. The affected proteins are primarily those of the sarcomere - the smallest functional unit of the heart muscle. Billions of these molecular motors work together to drive the heart.
Stefan Raunser is one of the world's leading experts on sarcomeres. His team in Dortmund was the first to obtain a high-resolution 3D image of the sarcomere in mouse heart muscle cells, revealing how the constituent muscle proteins interact, including those involved in cardiomyopathies.
Now, together with his American and European colleagues, he aims to go a step further and uncover how disease-associated protein variants alter the sarcomere and, consequently, the heart’s pumping performance. To achieve this, they will use heart muscle samples from affected patients.
Why hearts fail and how they can be repaired
Earlier treatment strategies for myopathies were limited to reducing afterload (thereby unloading the heart) and neurohormonal stimulation. However, the recent development of new drugs that directly modulate the function of sarcomeric proteins has opened entirely new therapeutic possibilities. The research consortium has already gained initial insights into how these substances work. The next step is to understand in detail how these drugs influence the structure, function, and physiology of the sarcomere.
‘Our state-of-the-art experiments range from ultra-high-resolution investigations to functional studies on individual cells and intact hearts. All of this serves the goal of better understanding why hearts fail and how to repair them most effectively. Together, we will identify the mechanisms of action and effects of various drugs, ultimately optimising therapy for those affected.’
About the Leducq Foundation
The Leducq Foundation is an international grant-making organization with a mission to improve human health through international efforts to combat cardiovascular disease and stroke. By forging scientific alliances that transcend national borders, and educating young researchers who thrive in an international context, we hope to promote the development of long-term collaborative relationships and to foster innovation in cardiovascular and stroke research, in order to change the way that patients with cardiovascular and neurovascular disease are diagnosed and treated.
