PRDM16 – a therapeutic target for heart failure

Heart failure is a life-threatening disease and is most common in patients who suffer from advanced-stage genetic cardiomyopathy. In this project we are focusing on the transcriptional regulator PRDM16 which is mutated in patients with cardiomyopathy and therefore a potential target for new therapeutic agents.

Coordination

Prof. Norbert Hübner
Max Delbrück Center for Molecular Medicine

PD Dr. Sabine Klaassen
Charité - Universitätsmedizin Berlin

Three questions for the team

Priv. Doz. Dr. Sabine Klaassen, Co-PI
Priv. Doz. Dr. Sabine Klaassen, Co-PI

1. What is the new idea behind your project?

The exact molecular role of PRDM16 in heart development and function is unknown. In a screen using PRDM16 zebrafish mutants five melanocortin receptor antagonists were identified to rescue the heart failure phenotype. The melanocortin system has been implicated in obesity-associated hypertension but not in cardiomyopathy. These critical findings prompt us to explore and target the melanocortin system in heart which is innovative but challenging.

2. How does your project fit in with BIH’s international work?

Development of therapies targeting cardiomyopathy is an urgent need. The great potential of this study is the combination of the molecular target identification of PRDM16 and characterization and treatment of a PRDM16 disease mouse model with a melanocortin receptor antagonist. Successful implementation of a small molecule treatment for cardiomyopathy would be a breakthrough in cardiology.

3. How might patients benefit from your results one day?

In the future, our results could help in the development of effective treatments for patients suffering from cardiomyopathy and prevent heart failure. This would enable targeted drug therapy before the onset of irreversible molecular changes.