New active ingredients for the treatment of heart failure
NRW-wide HI-FIVE research project launched
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Around four million people in Germany suffer from the life-threatening disease heart failure (cardiac insufficiency). For 50% of them, available medication is not an option or is insufficiently effective. Researchers and cardiologists at the Leibniz Institute for Analytical Sciences - ISAS, the Lead Discovery Center GmbH (LDC) and the Heart and Diabetes Center NRW (HDZ NRW) want to expand the treatment options for heart failure. They are working on the development of new active substances to specifically improve the care and quality of life of patients. Their new research project "HI-FIVE - GRK5 inhibitors for the treatment of various heart failure entities (HI-FIVE)" is being funded by the NRW state government and the EU with around 2.1 million euros.
In heart failure, the heart no longer pumps enough blood through the body. As a result, the organs are inadequately supplied with oxygen and nutrients. Those affected complain of a drop in performance, shortness of breath, fatigue and, in advanced cases, water retention in the tissue. But heart failure is not just heart failure, there are different forms: "While reduced cardiac output is the most common cause of heart failure in men, in women a reduced relaxation function of the heart muscle leads to reduced filling of the left ventricle," explains Prof. Dr. Tanja Rudolph, Senior Physician at the Clinic for General and Interventional cardiology / Angiology at the HDZ NRW.
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New therapeutic approach addresses key enzyme
The various manifestations of the disease make it difficult for half of those affected to receive adequate treatment with the drugs currently available. In a preliminary project, the researchers identified active substances that inhibit the key enzyme GRK5, which is upregulated in heart failure. The project partners in the HI-FIVE project now want to further optimize these GRK5 inhibitors in order to pave the way for a new, targeted therapy. "We will take gender- and age-specific aspects of heart failure into account in this research project. This is urgently needed, as age and female gender are still underrepresented in most preclinical and clinical studies," says Prof. Dr. Kristina Lorenz, Head of Translational Research at ISAS. The pharmacologist coordinates the HI-FIVE project.
Development of preclinical drug candidates
A great deal of research and development is still required before people with heart failure can benefit from a new therapeutic option in the future. The scientists and doctors are working closely together during the three-year preclinical research project to ensure that translation - the transfer of new findings into application - is successful. HI-FIVE is based on GRK5 inhibitor lead structures that the LDC has previously identified and optimized using high-throughput screening. The most promising candidates for good oral uptake and targeted action with as few side effects as possible are now being further developed in the HI-FIVE project. To gain a deeper understanding of heart failure, 500 patients will be examined at the HDZ NRW for one year with regard to the symptoms and severity of their disease. The scientists are investigating the effectiveness of GRK5 inhibitors in human heart muscle cells from stem cells and in mice. "At the end of the project, we want to reach the next important milestone towards clinical application with a preclinical drug candidate and thus create new treatment options for millions of patients with heart failure," adds Bert Klebl, CEO and CSO at the LDC.
Note: This article has been translated using a computer system without human intervention. LUMITOS offers these automatic translations to present a wider range of current news. Since this article has been translated with automatic translation, it is possible that it contains errors in vocabulary, syntax or grammar. The original article in German can be found here.
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