Watt Group | Translational Research in Osteoarthritis
Our group tests findings from the laboratory in human clinical studies, and runs experimental medicine studies and clinical trials relevant to osteoarthritis within the Arthritis Research UK Centre for Osteoarthritis Pathogenesis.
Fiona Watt also leads the Clinical Translation theme within the Centre for Osteoarthritis Pathogenesis facilitating the translation of findings across the Centre for patient benefit.
1. Joint injury cohorts: PREDICTING RISK OF POST-TRAUMATIC OA
Despite the immense burden of osteoarthritis (OA), there are currently no reliable biochemical tests to predict or diagnose early disease, and no medical treatments to slow or reverse it.
One of the obstacles to studying early OA is pinpointing the onset of an initially asymptomatic disease.
Joint injury is the major risk factor for OA: around 50% of those sustaining a significant knee injury will develop the disease. Models of joint tissue injury have allowed us to investigate the very earliest molecular changes following injury which predate, and perhaps lead to, the development of OA.
We have recently shown that specific markers of inflammation from our laboratory studies are also detectable immediately after human joint injury, which include pathways of regeneration or repair.
Individuals in KICK (the Knee Injury Cohort at the Kennedy) have been recruited immediately after their knee injury and are being followed for 5 years. We are testing whether measuring this initial molecular response in the joint might allow us to predict an individual's risk of future OA.
This includes work on protein, RNA and genetic markers in the cohort. In a further cohort, MenTOR (Meniscal Tear and Osteoarthritis Risk) we are examining the response following chronic meniscal injury and surgery.
We work closely with the Centre for Sport, Exercise and Osteoarthritis supporting OxKIC (Oxford Knee Injury Cohort), a further study of knee joint injury. We can also explore broader questions relating to arthritis risk in these cohorts.
Our work accurately measures markers in biological samples, particularly synovial fluid, typically using both in-house and commercial immunoassays. We therefore have an interest in bio-archiving and clinical databasing relating to clinical cohorts and biosamples. Our aim is to be able to define an individual's molecular risk of OA at the outset and to develop a 'risk profile' which assesses risk of future OA following joint injury. This work will hopefully pave the way for the testing of novel therapeutics in this area, with the aim of preventing post-traumatic OA.
2. EXPERIMENTAL MEDICINE STUDIES IN EARLY OA
We work closely with the Oxford Musculoskeletal Biobank and the Nuffield Orthopaedic Centre, with tissues donated by consenting individuals with osteoarthritis who are undergoing surgical procedures.
We are particularly interested in testing findings from the laboratory in appropriate experimental medicine studies, as a first step to translation to the clinic. This has included testing whether offloading the joint mechanically, by surgical or non-surgical means, affects experimental biomarkers in synovial fluid of these patients (in a collaboration with University of Utrecht), and the effects of novel drugs on pathways of interest in OA. We work closely with the Experimental Medicine and Rheumatology spoke of the Oxford Clinical Trials Research Unit (OCTRU) in running local studies.
3. Single and multi-centre clinical trials in OA
We recruit to interventional drug trials in osteoarthritis, particularly related to novel targets arising from the work in the Centre. Through the Centre and close working with the Thames Valley and South Midlands LCRN, we have expanded our work in this area to improve access for those wishing to participate in trials of medical treatments for osteoarthritis.
Given the typically slow progression of OA, an aim is to be able to stratify those with OA in the future, so treatments can be targeted at those at high risk of disease and/or progression. We are also proud to participate in UK-wide OA clinical trials through our links with the previous Arthritis Research UK Clinical Studies Group in OA, now part of the Musculoskeletal Disorders Research Advisory Group and the OA Special Interest Group, British Society for Rheumatology. We have recently taken part in HERO (a trial of hydroxychloroquine for hand osteoarthritis), and PROMOTE (a clinical trial of methotrexate for painful knee osteoarthritis), both funded by Arthritis Research UK, as well as commercially sponsored studies which target pain pathways in the disease. Our emphasis remains on academically led studies with an experimental medicine component.
- Tonia Vincent
- Nigel Arden
- Andrew Price
- Andrew Judge
- Luke Jostins
- Andrew Williams (KICK, Fortius Clinic)
- Keshthra Satchithananda
- Peter Cashman (Imperial College London)
- Philip Conaghan (Leeds)
- Floris Lafeber (UMC, Utrecht)
- Simon Mastbergen (UMC, Utrecht)
- Stefan Lohmander (Lund)
- Deborah Mason (Cardiff)
- Eleftheria Zeggini (Helmholtz-muenchen)