Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

New research at the Kennedy Institute reveals potential of a novel class of drugs for the treatment of rheumatoid arthritis.

cIAP inhibitors restore a healthy balance between inflammatory and regulatory T lymphocytes to reduce inflammatory arthritis

Research from Dr Richard Williams’ group at the Kennedy Institute reveals a potential new approach to limit inflammation in rheumatoid arthritis and increase the likelihood of drug-free disease remission. 

Anti-TNF drugs have dramatically improved the lives of many patients living with rheumatoid arthritis. Not all patients respond to therapy however, and most relapse if treatment is withdrawn. The new research published in Scientific Advances shows that targeting molecules called cIAPs in combination with a TNF inhibitor effectively treats inflammatory arthritis in animals, with sustained benefit even after treatment ends.

Speaking of the research Richard says, “Increasingly, patients with rheumatoid arthritis and other autoimmune diseases are seeking treatments that lead to sustained drug-free disease remission and this objective will most likely be achieved by early intervention and the use of combination therapy.” 

“We became interested in cIAPs because they control the biological pathways activated by TNF, a driver of inflammation in rheumatoid arthritis. Unexpectedly, we found that blocking cIAP1 and cIAP2 reduces the activity of some white blood cells which are known to promote inflammation in tissues”.

Dr Joanna Kawalkowska and co-workers in Richard’s team showed that the inhibitor of these cIAPs, a molecule by the name of GT13072, reduced the severity of disease in mice when administered continuously. However, when they combined GT13072 with the TNF inhibitor, Etanercept, the reduction in disease was sustained after treatment was stopped.

A more detailed look into the mechanism revealed that GT13072 decreased the amount of a protein known to regulate Th17 cell differentiation. This was accompanied by a marked increase in the joints of regulatory T cells, that promote healthy immune responses. 

“Resetting the balance between Th17 cells and regulatory T cells may underlie the long-term benefits of GT13072 when combined with Etanercept”, explains Richard.

The research suggests that inhibitors of cIAPs, which are already in clinical development for cancer, may also be suitable for management of rheumatoid arthritis and other autoimmune diseases. 

Anti-TNF Drugs

Similar stories

NIHR Fellowships awarded to NDORMS researchers

Congratulations to Eileen Morrow and Mae Chester-Jones who have received NIHR Doctoral Fellowships

ORUK Early Career Research Fellowship awarded to NDORMS researcher

Congratulations to Jack Tu who has been awarded an Orthopaedic Research UK Early Career Research Fellowship to explore the cause of knee pain after total knee replacement.

OCTRU - delivering answers to important clinical questions

The Oxford Clinical Trials Research Unit (OCTRU) has received NIHR benchmarking results and offers excellent value for money according to the report

Unhelpful thoughts about fracture symptoms hinder recovery

The importance of mindsets and feelings about fracture symptoms have been shown to be a key factor in recovery of musculoskeletal conditions.

Fat tissues can play a protective role against inflammation in the intestine

A new study in The EMBO Journal has revealed how fat tissues might provide a protective role in intestinal inflammation opening new lines of research into the treatment of inflammatory bowel diseases.

NDORMS researchers awarded Sir Henry Wellcome Fellowships

Kennedy Institute researchers Mariana Borsa and Edward Jenkins have both been awarded Sir Henry Wellcome Postdoctoral Fellowships, which give recently qualified postdoctoral researchers the opportunity to start independent research careers.