Identifying mechanisms and novel treatments of bone pain – closing the gap to the clinic.

Musculoskeletal pain from diseases such as arthritis and cancer in the bone affects the quality of life of millions and is a major societal burden. The current treatment options are opioids, non-steroid anti-inflammatory drugs and disease modifying drugs; however, these are often insufficient in providing an adequate pain relief. This is due to dose limiting side effects, the risk of misuse and addiction (opioids) and lack of efficacy. Thus, there is a strong unmet medical need. Drug development in pain has been hampered by a poor translation of preclinical data to the clinic and a lack of understanding of the underlying mechanisms. Therefore, in this project 4 academic beneficiaries, 3 industrial beneficiaries, 2 industrial partners and 4 academic partners join forces to create an outstanding and integrated training program for early stages researchers to increase the clinical translation of bone pain research and drug discovery and to provide novel mechanistic insight and potential therapeutic targets. We will develop fully humanized organ-on-a chip models of the painful bone disease microenvironment and we will use humanized mouse models, and tissue and liquid biopsies from patients to obtain clinically relevant data. Moreover, we will identify new disease mechanisms and potential treatment targets and explore the efficacy of clinical stage therapeutics in mouse models of the painful skeletal diseases osteoarthritis, rheumatoid arthritis, cancer in the bone and the rare bone disease, fibrous dysplasia. In an extensive training effort covering both specific research skills and transferable skills, the students will obtain an interdisciplinary, state-of-the-art and innovative training from the participants across sectors. The students will benefit from secondments with industrial partners and with some of the foremost pain researchers in Europe.