Identification of disease-relevant epigenetic targets for the development of novel therapeutic strategies for the Complex Regional Pain Syndrome (CRPS) and Osteoarthritis (OA).

Our aim is to identify novel epigenetic changes in patients with Complex Regional Pain Syndrome (CRPS) and Osteoarthritis (OA) by high-throughput techniques. Biocomputational analysis will then identify epigenetically regulated key pathways in the pathogenesis of CRPS and OA, which then can be modified to alter the overall disease outcome and to develop novel epigenetic-based therapeutic strategies.

Grant Application

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The aim of our research is to identify novel epigenetic changes in patients CRPS and OA. For the identification of epigenetic modifications we are using high-throughput techniques. Biocomputational analysis will then identify epigenetically regulated key pathways in the pathogenesis of the selected diseases, which then can be modified to alter the overall disease outcome. The long-term goal is to develop novel epigenetic-based therapeutic strategies for patients with CRPS and OA.

The two diseases were selected because of our clinical and translational expertise in these areas. Furthermore, the Center of Experimental Rheumatology is an internationally renowned institution for epigenetics in rheumatic diseases and has a strong background in translational science including the development of novel, targeted therapies for rheumatic diseases.

  • Goal:
    Our aim is to identify novel epigenetic changes in patients with CRPS and OA by high-throughput techniques. Biocomputational analysis will then identify epigenetically regulated key pathways in the pathogenesis of CRPS and OA, which then can be modified to alter the overall disease outcome and to develop novel epigenetic-based therapeutic strategies.
  • Issues:
    Despite increasing research in the field of CRPS and OA the underlying mechanisms of these conditions remain unclear. The idenfication of epigenetic changes is a relatively new method to investigate the pathogenesis of diseases. Epigenetically regulated key pathways potentially be modified to alter disease outcome and to develop novel therapeutic strategies.
  • Research:
    We will analyze cells from skin biopsies (CRPS) respectively synovial fibroblasts, chondrocytes, blood cells and serum (OA) for epigenetically regulated signyling pathways with high-throughput techniques.
  • Phases:
    We will establish a biobank with patient samples and controls. These samples will be used for a biocomputational analysis to identify epigenetically regulated key pathways.
  • Budget:
    This project is funded by Balgrist Stiftung.
  • Progress:

Embedment in Balgrist research

The present research at The Balgrist will be considearbly enhanced. The Department for Physical Medicine and Rheumatology will be able to conduct basic musculoskeletal research in close cooperation with the Department for Rheumatology of the University Hopsital Zurich (USZ). The know-how brought in by the colleagues from the University Hospital, the (state-of-the-art) infrastructure of the Balgrist Campus and the closness to the clinic complement each other in an ideal manner.

Innovation

In the last years, the ability to examine epigenetic modifications has given rise to a wealth of new information concerning the contribution of epigenetically regulated signaling pathways to the pathogenesis of human disease. These epigenetic modifications are composed of single or a combination of post-translational modifications placed on nuclear proteins, methylation of DNA and transcriptional regulation by non-protein coding RNAs (short non-coding RNAs such as miRNAs or long non-coding RNAs). Many of these regulatory pathways were previously unknown. The knowledge of epigenetic modifications will elucidate the contribution of signaling molecules (enzymes) in key signaling pathways. This potentially lead to new diagnostic and therapeutic approaches for diverse and difficult to treat human diseases.

Prof. Dr. Oliver Distler is a Professor for Rheumatology at the medical faculty of the University Zürich and the director of the Department of Rheumatology at the University Hospital Zürich (UHZ). He has been the director since 2016 and at the university hospital since 2006.

The main focus of Prof. Distler's research has been on systemic sclerosis. Amongst the projects he has been involved with, is the validation of a highly sensitive imaging process that uses a special anti-body. This process can identify the onset of the disease in its early stages at a molecular level.

Patient benefit

Prospective and current patients perceive The Balgrist as a proficient center for the treatment and research of musculoskeletal disease. The clinical and scientific collaboration with the Department of Rheumatology (USZ) will create synergies which will ultimately be of great benefit to the patients.