The RESET button to cure systemic sclerosis

RESET: Restoring the balance in Systemic sclerosis by Targeting macrophages

Researchers from UMC Utrecht and argenx collaborate in this project to find a potential therapeutic target to address systemic sclerosis (SSc). We aim to intercept the fibrotic cycle in SSc by targeting immune cells. SSc is a severe autoimmune disease with high morbidity and mortality, affecting 80.000 patients in the EU. SSc is characterized by generalized fibrosis in the skin and internal organs, and no effective treatment options exist to date. The lack of treatment options comes from the fact that the pathological mechanism of disease is not fully understood. In this project we focus on the interaction between immune cells and tissue cells. We will study how macrophages regulate tissue repair, and how disturbed collagen deposition that is found in SSc contributes to dysregulated signaling. Next, we will test if targeting of macrophages with specific agonists limits fibrosis in a newly developed 3D human skin model for SSc. Together, this will reveal if these specific agonists indeed have potential therapeutic value in SSc.

After completion of this project we will (1) have detailed knowledge of how macrophages regulate fibrosis, (2) know whether our target protein is a justified clinical target for SSc, and (3) whether the tested agonists may have future potential in SSc treatment. Furthermore, we will have developed a primary human skin models for SSc that supports future testing of therapeutics in human preclinical models.

Summary
Systemic sclerosis is a progressive auto-immune disease with no existing curative treatment options. Ongoing inflammation and tissue repair in systemic sclerosis causes fibrosis of skin and internal organs. In this project we aim to intercept the fibrotic cycle and find a potential therapeutic target for systemic sclerosis.
Technology Readiness Level (TRL)
1 - 3
Time period
36 months
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