About 4 million individuals in Germany suffer from chronic heart failure, a life-threatening condition in which the heart no longer pumps properly. Depending on the type of heart failure, different active substances may be used for treatment. However, there is currently only one class of active substances that is suitable for several forms of heart failure. Because patients with heart failure often also suffer from chronic kidney disease or diabetes, new drugs are needed that also take these comorbidities, age and gender into account.
In an earlier research project, scientists at ISAS in Dortmund were able to show that G protein-coupled receptors (GPCRs) play an important role in heart function. The GPCRs in the cell membrane of the heart transmit signals to the interior of the cell to control, for example, the force of the heartbeat and heart rate. In heart failure, GPCRs are often permanently stimulated, causing certain enzymes such as G protein-coupled receptor kinases (GRKs) to make the receptors less responsive to signals. Chronic overstimulation can thus reduce heart function and lead to heart failure. Together with the drug discovery company Lead Discovery Center GmbH, ISAS scientists have identified a drug that inhibits the key enzyme GRK5, which is upregulated in heart failure. The aim of the new project ‘HI-FIVE – GRK5 inhibitors for the treatment of various heart failure entities’ ('HI-FIVE – GRK5-Inhibitoren zur Therapie verschiedener Herzinsuffizienz-Entitäten') in cooperation with the Herz- und Diabeteszentrum NRW (as the executing agency of Ruhr University Bochum) is now to develop new GRK5 inhibitor-based active substances that also take into account gender- and age-specific aspects of the disease.