The most common reason for the failure of new therapies in early phase drug discovery is lack of efficacy. A major part this is due to the unsolved problem of how to demonstrate that drug pathways have been engaged early in target tissues in humans. Furthermore, it remains unclear how to measure drug efficacy following a therapeutic intervention because pathology occurs in tissues, whereas experimental readouts focus on easy to access cells in the blood. The Clinical Pathology platform aims to provide the underpinning technology, to use pathology-based biomarkers to de-risk therapeutic development and accelerate delivery of new medicines.
By focussing on human tissues obtained via minimally invasive techniques, the platform will deliver good clinical practice (GCP) compliant analysis of human tissues to be used in innovative clinical trials in which mechanistic cellular markers are used as endpoints for proof of efficacy. This platform builds on and extends to other disease indications in the Kennndy Institute, the successful pilot of the Arthritis Therapy Acceleration Programme (A-TAP) which has provided evidence that such a strategy can work.
- Clinical Pathology works closely with the Tissue Biology platform, particularly in use of the Hyperion Imaging System and to facilitate new experimental medicine studies, as well as with the Data Science Platform and investigators in the Clinical Translational and Experimental Medicine Theme.
- Beyond supporting groups at the Kennedy Institute in their research programmes, the Platform works with other research units both within and external to the University. In particular, the Clinical Pathology Platform works closely in collaboration with Prof Andrew Filer (University of Birmingham) who leads the Birmingham Tissue Analytics, Prof Adam Croft (University of Birmingham) who leads the MRC Partnership TRICIA (Tissue Research In Childhood Arthritis) and Prof Holm Uhlig (University of Oxford) who leads the Janssen funded CAROGRAPHY consortium. It also works closely with members of the RACE Consortium from the Universities of Glasgow, Newcastle and Birmingham.
Anti-tumour necrosis factor therapy for early-stage Dupuytren's disease (RIDD): a phase 2b, randomised, double-blind, placebo-controlled trial
Nanchahal J. et al, (2022), The Lancet Rheumatology
Clinical and molecular associations with outcomes at two years after acute knee injury: a longitudinal study in the Knee Injury Cohort at the Kennedy (KICK)
Garriga C. et al, (2021), Lancet Rheumatology
Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases.
Korsunsky I. et al, (2022), Med (N Y), 3, 481 - 518.e14
IL-1-driven stromal-neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies.
Friedrich M. et al, (2021), Nat Med, 27, 1970 - 1981
Targeting synovial fibroblast proliferation in rheumatoid arthritis (TRAFIC): an open-label, dose-finding, phase 1b trial
Pratt AG. et al, (2021), The Lancet Rheumatology, 3, e337 - e346
Small research facilities