PM.20.052 – Personalized medicine in osteoarthritis

Route: Personalised medicine: the individual at the centre

Cluster question: 101 Can we model the human body and use smart technologies for health, nutritional, and toxicity research, drastically reducing the use of laboratory animals at the same time?

Osteoarthritis is one of the most common chronic diseases characterized by gradual joint deterioration. The disease presentation is highly variable depending, amongst others, on gender, (epi)genetic make-up, and life style and cannot be cured. It has become clear that a one size fits all treatment is doomed to fail as underscored by failed trials in the past. Failures have been attributed to lack of patient stratification due to neglecting the large inter patient variation. In the past years (epi)genetic studies have revealed distinct risk factor profiles associated with the development and progression of osteoarthritis. It has remained, however, largely unclear how these profiles contribute to the initiation and progression of the disease mechanistically and impact the efficacy of disease modifying osteoarthritic drugs (DMOADs). Furthermore, it can be expected that these genetic risk factor profiles impact the development of new medication and are instrumental in selecting the optimal treatment for the individual patient. To address these issues we intend to engineer genetically distinct so-called joint-on-chips using iPS cells with distinct genetic risk profiles. These joint-on-chips are micro-physiological mimics of the moving human joint which can be triggered to develop key features of osteoarthritis using established disease triggers like synovial inflammation and cartilage trauma. Non-destructive imaging modalities will be incorporated in the disease model enabling the longitudinal monitoring of disease progression. We will use the model to study the impact of genetics on development of osteoarthritis-on-chip. Furthermore, we will use these models to identify biomarker profiles characteristic for subsets of patients and use the models for testing new and/or existing drugs for their efficacy in treating the disease depending on the genetic risk profile. The joint-on-chip will proof a valuable asset to identify dearly needed DMOADs and will contribute to the reduction in the use of experimental animal models in drug development.

Keywords

genetic risk factors, joint-on-chip, osteoarthritis, personalized treatment

Other organisations

Erasmus Medical Center (EMC), Leiden Universitair Medisch Centrum (LUMC), Radboud Medical Center (RUMC), UMCU

Submitter

Organisation University of Twente (UT)
Name Prof. dr. H.B.J. (Marcel) Karperien
E-mail marcel.karperien@utwente.nl
Website www.utwente.nl/tnw/dbe