Watt Group | Translational Research in Osteoarthritis
Our group tests findings from the laboratory in human clinical studies, and runs 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, facilitating the translation of findings across the Centre to patient benefit.
1. Joint injury cohorts: studying early OA risk
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.
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 later disease.
This work includes identification of protein, RNA and genetic markers from the cohort. In a further cohort, MenTOR (Meniscal Tear and Osteoarthritis Risk) we will examine this response following chronic meniscal injury and surgery; the effects of modifying or altering joint loading by surgical or non-surgical means, and measuring reparative pathways are also a focus.
We work closely with the Centre for Sports, Exercise and Osteoarthritis, where recruitment to a further cohort of knee joint injury, OxKIC (Oxford Knee Injury Cohort) is underway.
Our work quantifies 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. We can also explore broader questions relating to arthritis risk in these cohorts.
Our aim is to be able to measure and add an individual's molecular risk to a 'risk profile', to define their risk of future OA following joint injury. We hope this work will also identify new molecules as potential targets for therapies.
2. Biomarkers for early OA
A frequent clinical scenario is the development of symptoms of OA before abnormalities can reliably be seen on X-ray, the current 'gold standard' test.
Our work aims to define and quantify specific molecular or imaging changes which reliably predate X-ray change: detecting early disease may, in the same way as has occurred in inflammatory arthritis, allow us to intervene in a timely way to prevent disease progression and joint damage.
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.
3. Single and multi-centre clinical trials in OA
We continue to improve our capability to recruit to interventional drug trials in osteoarthritis locally, particularly related to novel targets arising from the Centre.
Given the typically slow progression of OA, we hope in the future to target new treatments to groups at high risk of disease and/or progression. We are also proud to participate in UK-wide OA clinical trials.
We have close links with the OA Special Interest Group, British Society for Rheumatology and Arthritis Research UK Clinical Studies Group.
With funded posts through the Centre, we have expanded our work in this area to improve access for those wishing to participate in trials of medical treatments for osteoarthritis.
We have recently taken part in HERO (a trial of hydroxychloroquine for hand osteoarthritis), and are currently recruiting to the PROMOTE clinical trial of methotrexate for painful knee osteoarthritis, both of which are funded by Arthritis Research UK.
We work closely with the Thames Valley and South Midlands LCRN, who supports some of this work.
- Tonia Vincent
- Nigel Arden
- Andrew Price
- Andrew Judge
- Raashid Luqmani
- Philippa Hulley
- Andrew Williams (KICK, Fortius Clinic)
- Adrian Lim
- Adam Mitchell
- Keshthra Satchithananda
- Peter Cashman (Imperial College London)
- Philip Conaghan (Leeds)
- Floris Lafeber
- Simon Mastbergen (UMC, Utrecht)
- Stefan Lohmander (Lund)