Decode and Cure primary Focal Segmental Glomerulosclerosis

Introduction

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.

Overview of FSGS

FSGS is the most common glomerular cause of end-stage renal disease characterized by scarring of the glomerular kidney filters and podocyte 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.

Objectives of CureFSGS

CureFSGS will establish a new strategy to identify key factors in FSGS:

1. Molecular Classification
   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.

2. Decoding Immune Mediators
   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.

3. Precision Targeting
   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.

Conclusion

Together, CureFSGS will set the stage to finally understand and treat FSGS effectively.