Strategies for therapeutic targeting of the Aldosterone-Mineralocorticoid Receptor signaling pathway

• Applicant: Privatdozent Dr. Achim Lother
• Subject Area: Pharmacology
• Term: from 2021 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 470188766

The physiological role of aldosterone is to control salt-water homeostasis by acting on the mineralocorticoid receptor (MR) in renal epithelial cells. However, in the past years, a number of studies covering the full spectrum from basic science to clinical trials indicated a role for MR in a broader range of pathological conditions and the reciprocal dependence of different organ systems. These include widespread diseases such as chronic kidney disease, diabetes mellitus, lung disease, liver disease, or cancer that are associated with substantial morbidity and mortality in Germany and the EU. Exploring the therapeutic potential of targeting the aldosterone-MR signaling pathway is therefore timely and of high socioeconomic impact. Currently available MR antagonists are already well established in the treatment of chronic heart failure but their use is limited by substantial adverse effects, e.g. hyperkalemia. Innovative approaches for therapeutic targeting are needed that should be specific for the MR signaling pathway and selectively aiming at its pathological effects in the relevant tissues and cell types. The aim of this scientific network is to connect scientific activities in Germany and the EU to achieve a synergistic output concerning MR research. To this end, we will develop a structured training program for early stage researchers in the aldosterone-MR field. The interdisciplinary nature of this venture requires close collaboration of researchers from different backgrounds. We will bring together basic scientists with translational or clinical researchers to foster exchange, establish new interactions, and initiate collaborative research projects. Together, we will propose a roadmap of how to move from MR-related basic to translational research and discuss the clinical application of MR antagonists in new indications.

• DFG Programme: Scientific Networks