Complex models to guide drug development for systemic sclerosis
Researchers from UMC Utrecht, Radboud UMC and argenx collaborate in this project to develop COMPASS: a modular and scalable SSc-skin like system that replicates SSc pathology. COMPASS builds upon the solid fundament of existing human models in RadboudUMC and UMC Utrecht. In close collaboration with drug developer argenx, we will improve and combine features of both already existing models and tailor them to the preferred scalability and complexity needed for drug development.
Systemic sclerosis (SSc) is a severe auto-immune and fibrotic disease with high morbidity and mortality, without effective treatment options. SSc pathophysiology is complex, involving the immune system, vasculature and stromal cells. How the interplay of these three compartments leads to fibrosis is not well known. Drug development is hampered by lack of translational preclinical models which encompass all these three compartments, fully addressing disease complexity, which is imperative to address the high medical need in SSc.
We will stepwise include all three compartments representing SSC pathology into the existing models. Each added component will be benchmarked and cross validated in both Utrecht and Nijmegen to ensure reproducibility. We will validate the response of COMPASS models to current drugs used to treat SSc and other fibrotic diseases.
The outcome of the project is COMPASS: a series of modular and scalable human preclinical models for SSc. Due to its scalability the models will be suitable for both mechanism-of-action studies and drug validation. As such, COMPASS will support much needed future drug development for patients that currently lack effective treatment options.
