June 2014

UCD Scientist Secures Prestigious Rheumatology Research Award

Wed, 18 June 14 09:43

Dr Ursula Fearon, senior research scientist at St Vincent's University Hospital has secured a prestigious research award which was announced last week at the EULAR (European League Against Rheumatism) Annual European Congress in Paris.  One of only five awards, the highly competitive ASPIRE research grant is funded by Pfizer Europe and aims to support research in autoimmune diseases within Rheumatology and Dermatology.

"The Pfizer European ASPIRE award will allow us, for the first time, to perform unique studies to examine how blocking of the JAK signalling pathway with tofacitinib, will impact on the inflammation of synovial tissue and bone destruction in rheumatoid arthritis."

Dr Fearon has established an international reputation in the area of inflammation, metabolism and their signaling pathways. She has developed a unique model of rheumatoid arthritis (RA) using the joint lining tissue from RA patients, that more closely reflect the in-vivo joint environment, to examine potential new treatments.  Using these ‘pre-clinical proof of concept models’ it is possible to dissect out the complex signaling pathways involved in inflammation and metabolism in RA.

Current medicines work for many, but not all patients and side effects may limit their use therefore new treatment strategies are needed. Tofacitinib, a new drug developed by Pfizer, interferes with the JAK-STAT signalling pathway, a key inflammatory pathway involved in the pathogenesis of RA. Importantly, while a number of studies have been performed in RA models, to date none have examined the effect of tofacitinib on RA synovial tissue.

This ASPIRE award will enable Dr Fearon's team to examine the inhibitory effect of tofacitinib in cells and tissue obtained from patients with active RA to test if blocking the JAK-STAT pathway with tofacitinib reduces inflammation and bone damage.  This will be the first study to examine the effect of Tofacitinib in RA synovial biopsies cultures obtained from the site of inflammation under direct visualisation. These synovial biopsies will be established immediately from surgery as ex vivo whole tissue explant cultures which maintain the architecture and cell-cell contact of tissue and spontaneously release pro-inflammatory mediators, therefore more closely reflects the in vivo environment. RA synovial explants will be treated with tofacitinib and pro-inflammatory responses assessed, and patients will be followed-up clinically in parallel. It will be particularly important to identify if tofacitinib has significant effects in RA explant cultures from patients who on clinical follow-up do not respond to current treatment strategies. Furthermore, Dr Fearon will examine the effect of tofacitinib on a specific cell type in the joint called the ‘synovial fibroblast’ which is the main cell involved in invading and destroying the cartilage and bone, thus leading to functional disability.