Prevent-SSc

Early Detection and Prevention: A New Approach to Systemic Sclerosis (SSc)

Systemic sclerosis (SSc) is a severe autoimmune disease that causes hardening and scarring of the skin and internal organs, and it has the highest mortality rate of all rheumatic diseases. Until now, treatment has focused on cases in which the disease is already advanced. The PREVENT-SSc project, led by a team at the University of Zurich, aims to change this approach. The goal is to detect disease progression early and to prevent damage before it occurs. To this end, the team aims to identify risk factors and find new therapeutic targets for early treatment.

At the heart of the project is identifying people who are in the early stages of SSc but at high risk of rapid disease worsening. The team plans to combine various factors, such as clinical markers, blood tests, and mechanical skin assessments, to develop an individual risk scoring system that can predict the likelihood of disease progression. This approach enables more targeted treatment that can begin even before severe symptoms appear.

To achieve long-term progress, the team is also investigating molecular changes in early-stage SSc. Using cutting-edge technologies such as single-cell RNA sequencing and proteomics, the researchers aim to create a “molecular map” of the early stages of the disease. By studying these molecular changes, they hope to identify specific therapeutic targets that could stop the disease from progressing. The idea is to find new treatment targets that can positively influence the course of the disease.

Selected Research Results

The project kicked off in December 2024. At this first meeting, the interdisciplinary consortium laid the key foundations for its collaboration. Another milestone followed in October 2025, when a consortium meeting served to present progress and to refine the project’s methods. These regular meetings ensure coordination among all partners. Patients are also actively involved as research partners.

Two study protocols—one for the use of biosamples and one for the NIMBLE clinical study—are currently under ethics review. Among other things, the NIMBLE study includes a newly developed test for the standardized measurement of skin properties. In addition, agreements on the exchange of samples have been concluded between USZ, UZH, ETH Zurich, and the University of Freiburg (Germany).

Based on long-term data from the international EUSTAR registry, a comprehensive database containing clinical follow-up data from patients with systemic sclerosis, a clinical risk model was developed using machine learning. It helps to estimate early on which patients are at increased risk of organ involvement.

For clinical use, a standardized NIMBLE test protocol was developed that captures key mechanical properties of the skin, such as stiffness and deformability, in about 40 minutes. Using a dedicated computer model that captures the influence of material parameters on the measurement results in silico, the team was able to assess the sensitivity of the clinical procedure.

At the molecular level, new fluorescent probes were developed that make it possible to precisely measure the activity of key enzymes in complex biological environments. These include LOXL2 (lysyl oxidase-like 2), an amine oxidase that plays an important role in connective tissue synthesis, and vascular adhesion protein-1 (VAP-1), which is associated with inflammatory processes, among other things. This method opens up new possibilities for diagnostics and research.

A major advance was achieved through single-cell analyses of clinically normal-appearing skin from individuals with pre-SSc. Even at very early stages, connective tissue cells show marked changes (activation of fibroblasts). At the same time, changes in immune status occur that point to the active recruitment of immune cells. The results suggest that the interaction between the stroma and the immune system is a key driver of the disease process and precedes the actual hardening of the tissue. This opens an early window for potentially preventive therapies. In addition, an ex vivo model using precision-cut skin slices was developed. This model realistically reproduces the complex tissue structure and makes it possible to test new therapeutic approaches under controlled conditions.

Significance for Zurich as a Research Hub

The project brings together experts from rheumatology, chemistry, biology, bioinformatics, and proteomics in an interdisciplinary consortium. PREVENT-SSc not only strengthens precision medicine in the field of autoimmune diseases but also positions Zurich as a center for research into and prevention of chronic diseases. Its preventive approach can also serve as a model for the treatment of other complex diseases.

Infection / Immunology