CONTRACT
Researchers from the groups of Folkert Asselbergs and Magdalena Harakalova (UMC Utrecht), Jeroen Bakkers (Hubrecht Institute) and Frédéric Vaz (Amsterdam UMC) receive €936.000 from the ZonMw Open Competition for their CONTRACT project. They will study how mutations in the PLN gene affect the energy supply of the heart. The results will contribute to the development of new treatment strategies for heart muscle diseases.

Cardiomyopathies are a group of diseases that severely affect the heart muscle, which can result in heart failure and death. The phospholamban R14-deletion (PLN-R14del or PLN) is the most common mutation related to cardiomyopathy in the Netherlands. Carriers of this mutation have a high risk of developing heart failure. However, despite decades of research, very little is known about the mechanisms of this devastating disease.

Disease models
With the CONTRACT project, researchers from the UMC Utrecht, the Hubrecht Institute and the Amsterdam UMC will investigate the consequences of PLN mutations for the heart. To that end, they have developed two disease models – a human stem cell- and a zebrafish model.

Using these models, the researchers aim to elucidate how mutations in PLN can affect the energy supply of the heart. The results will provide insights into the mechanisms underlying pathological changes in the heart, and help identify new risk factors and opportunities to identify treatment strategies.

New positions
The funding from ZonMw allows the collaborative project to continue for four years, during which there will be room for 2 PhD students and a postdoc. Additionally, the grant enables the purchase of a new device for the screening of heart muscle cells and zebrafish larvae. 

PROPER-THERAPY
A multi-centre PROPER-THERAPY team by Jolanda van der Velden (VUMC), Riekelt Houtkooper (AMC), Diederik Kuster (VUMC), Magdalena Harakalova (UMCU), Frank van Steenbeek (UU/UMCU), Miranda Nabben (MUMC), Daphne Merkus (Erasmus MC), Andreas Dendorfer (LMU Munich), and Michiel Helmes (Ionoptix) received €859.014 from NWO Human Measurement Models 2.0 to perform disease modelling and treatment testing on 2D/3D models of iPSC-cardiomyocytes for carriers of MYBPC3 and VLCAD mutations causing cardiomyopathies.

Genetic heart diseases in a dish
Genetic cardiomyopathies, such as hypertrophic cardiomyopathy (HCM), are a highly prevalent global problem. HCM is a heterogeneous disease: the severity, as well as the response to treatment, varies tremendously even between the patients with the same genetic defect. Within this project, severe phenotypes of HCM will be mimicked using stem cell technologies to further improve human heart models.

PROPER-THERAPY will validate stem cell models by comparing them with patient cardiac material and utilizing patient clinical records. This model is going to be subjected to different metabolic stressors and medicines to validate the effectiveness of stem cell therapies for personalized patient treatments.

Artificial intelligence (AI)
AI will be used to further improve the high-throughput system for treatment testing. The validation of such human heart models is an essential first step towards the clinical application of stem cell technologies for personalized medicine in genetic cardiomyopathies.

Read more about PROPER-THERAPY (in Dutch)
Read more about CONTRACT (in Dutch)