CureFSGS · Decode and Cure primary Focal Segmental Glomerulosclerosis

Kidney diseases are a worldwide rising major health problem associated with an excess risk for cardiovascular disease and reduced life expectancy. While general risk factors for kidney diseases such as diabetes and hypertension are being addressed through numerous research efforts, causes of specific glomerular kidney diseases, especially Focal Segmental Glomerulosclerosis (FSGS), remain poorly understood. FSGS is the most common glomerular cause of end stage renal disease characterized by scaring of the glomerular kidney filters and podocytes loss. Until now, the development of specific therapies has been hindered by the poor stratification of FSGS entities and the lack of understanding of immune mediated forms of FSGS. CureFSGS will establish a new strategy to identify key factors in FSGS: First, CureFSGS will develop a molecular classification of FSGS entities by utilizing a worldwide unique kidney sample repository/ registry combined with a novel analysis pipeline of single cell analytics, multiplex imaging and machine learning-aided image analysis to guide clinical decision making and to provide novel molecular insights. Second, CureFSGS will precisely decode immune mediators of FSGS and systematically map the podocyte response towards immune actions by devising a novel complementary platform of immune cell analytics and podocyte in vitro, ex vivo perfused kidney, in vivo as well as human organoid systems. Third, CureFSGS will ultimately precision target the identified immune cells, soluble immune factors or podocyte injury pathways by newly developed cell-specific AAV- and nanobody strategies. Together, CureFSGS will set the stage to finally understand and treat FSGS effectively.