Pathogenic mechanisms and therapeutic targets
In order for any new treatments to be implemented in the NHS there is a need to generate evidence for clinical and reimbursement decision-makers that implementation would not only provide clinical benefit, but would result in cost efficiency savings within financially stretched healthcare systems. The GCA diagnostic and treatment pathways exhibit substantial opportunities for such improvements.
GCA is challenging therapeutic area for clinical trialists. The disease presents acutely, requiring immediate treatment (which can hamper trial recruitment). Patients are often elderly and have comorbidity (again impacting on recruitment). The disease is heterogeneous and currently lacks robust biomarkers beyond simple measures of inflammation. Validated outcome measures that capture relevant outcomes and are sensitive to change are yet to be developed. Collectively, these have contributed to the historical reluctance of industry to undertake clinical trials.
Projects
Genetic studies
- Unravelling the genetic architecture of GCA through genome-wide association studies (Dr Elisabeth De Smit, Ophthalmology Registrar and Research Fellow, King’s College Hospital NHS Foundation Trust, and King’s College London)
- Genome-wide association study of PMR (Professor Jenny Barrett, Professor of Genetic Statistics, University of Leeds; Dr Sarah Mackie; Professor Ann Morgan; Miss Charikleia Chatzigeorgiou, PhD student, University of Leeds)
- Marie Skłodowska-Curie Actions, Innovative Training Network, HELICAL, work package 2: identification of key pathogenic pathways suitable for therapeutic targeting in GCA (Professor Ann Morgan, with multiple European partners)
Macrophage polarisation
- Determining the role of multinucleated giant cells in GCA (Dr Gary Reynolds, Clinical Fellow, University of Newcastle Upon Tyne, The Newcastle Hospitals NHS Trust)
- Identification of novel macrophage polarisation markers and evaluation in GCA (Professor Ann Morgan; Dr Sarah Mackie; Dr Aruna Chakrabarty; Dr Euan Baxter, Research Associate, University of Leeds; Miss Amy Graham, PhD student, University of Leeds)