Diabetic kidney disease (DKD) poses a significant global health challenge as the leading cause of chronic kidney disease (CKD) and a major contributor to end-stage renal disease (ESRD). With 20% of DKD patients progressing to ESRD, this condition is associated with tremendously increased morbidity and mortality. The pathophysiology of DKD is complex and incompletely understood, and the number of treatment options remains low. The DECODE-DKD project, led by Principal Investigator Christoph Kuppe at the University Hospital RWTH Aachen, Germany, aims to address these issues through a patient-centric research approach.
Our objectives are to create a detailed, spatially resolved molecular map of human DKD, providing deep insights into its pathophysiology, and to identify and dissect therapeutic pathways and signaling networks for new drug target discovery. Additionally, we aim to use patient-derived in-vitro models to validate these targets, ensuring their potential effectiveness in treating DKD. By employing advanced spatial and single-cell molecular techniques, we intend to generate a comprehensive map of DKD at the single-cell level, leading to innovative therapeutic approaches.
The vision of DECODE-DKD is to utilize these novel spatial and single-cell multi-omic technologies to generate a blueprint and predictive model of DKD. This unbiased map will serve to generate testable hypotheses with spatial and temporal coordinates at single-cell resolution. To identify disease-relevant pathways and novel druggable targets, in-vitro and in-vivo genome editing approaches will be employed, combined with high-throughput screens. In-vitro assays with human-derived kidney organoids will be used to screen potential compounds, facilitating the development of novel therapeutics. This highly ambitious interdisciplinary proposal requires the expertise of biomedical engineers, computational biologists, biomedical researchers, and physician-scientists. The knowledge and outcomes generated by DECODE-DKD will be transformative, providing a significant step forward towards novel drug targets and precision medicine for the treatment of diabetic kidney disease using a systems medicine approach.
