Schwarz, Günter | Köhler, Felix - C 12

Acute kidney injury (AKI) is a frequent threat for our patients causing substantial morbidity and mortality. Interestingly, specific diets have shown an immense potential to prevent kidney damage in rodents. Using a multi-layered omics approach we detected sulfur metabolism as a common and cell-type specific mediator of diet-induced kidney protection. More importantly, the diet-induced changes in sulfur metabolism are conserved in human kidneys of donors adhering to beneficial diets in the setting of living kidney donation. MBK2910, in turn, promises to mimic these well-known diet-induced protective effects due to its unique mode of action in sulfur metabolism. Triggered by this novelty, inventive activity, and industrial applicability in medicine, the University of Cologne has registered MBK2910 as a novel drug for AKI by for a patent.

To pave the way for a successful clinical translation, we will now examine the downstream metabolic changes in the rescue of ROS-induced cell death mediated by MBK2910 in-vitro. In parallel, efficacy, safety and tolerability of MBK2910-treatment will be studied in rodent models of ischemia, sepsis and drug-toxicity caused AKI in vivo. This will be accompanied by toxicological testing of MBK2910 in accordance with the guidelines of EU Regulation 536/2014. And finally, we will develop the large-scale, GCP-compliant production of MBK2910 in this project. In aggregate, MBK2910 has an immense potential for our therapeutic toolkit in AKI.

One of the key organs affected by aging is the kidney. A pivotal problem in aging-associated kidney disease is the elevated risk of acute kidney injury (AKI). Despite its considerable burden and socioeconomical impact, effective therapeutic approaches are elusive. MBK2910 renders cells ROS resistant and promises to mimic the well-known diet-induced effects in organ protection. Thus, MBK2910 may be substantial addition to our therapeutic armamentarium in kidney disease and even beyond.

1. Rescue of ROS-induced cell death mediated by MBK2910 allowing to determine downstream metabolic changes in-vitro.
2. Efficacy, safety and tolerability analyses of MBK2910 in rodent models of ischemia, sepsis and drug-toxicity caused AKI in-vivo.
3. Toxicological testing of MBK2910 in murine AKI models in accordance with the guidelines of EU Regulation 536/2014.
4. Development of large-scale, GCP-compliant production of MBK2910.

Please find more information about Prof. Schwarz´ research and work at Schwarz Lab and about Dr. Köhler´s research here. 

• CMMC Cologne
• Institute for Biochemistry
• SFB 1218

• Center for Molecular Medicine Cologne (CMMC)
• Dept. II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
• Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany