A new study by University of Oxford researchers has identified potential new therapeutic targets for the treatment of inflammatory bowel disease (IBD), giving hope to millions of patients with ulcerative colitis or Crohn’s disease.
The research team from the University’s Kennedy Institute of Rheumatology and Translational Gastroenterology Unit (TGU) were supported by the NIHR Oxford Biomedical Research Centre (BRC),
Published in Nature Medicine, the research has defined a subset of patients with IBD that do not respond to several current therapies.
The research set out to explore the different cellular and molecular processes that underlie inflammation in the tissue of patients who do not respond to treatment. They found that patients with ulcers who had increased activation of fibroblasts and expansion of the vascular system, and a high number of neutrophils in the inflamed intestine responded poorly to treatments.
Fibroblast activation and accumulation of neutrophils were driven by increased signalling from the cytokine IL-1R, which suggests that blocking IL-1 may benefit those individuals with deep ulceration and who do not respond to several different current therapeutics.
Patients with IBD saw a breakthrough when anti-TNF therapy was shown to be an effective treatment, but up to 40% of patients with IBD don’t respond to the therapy.
“Anti-TNF is not effective in all patients with IBD,” said Professor Fiona Powrie, Director of the Kennedy Institute and lead researcher on the study. “One of the major challenges has been to understand the cellular mechanisms and inflammatory pathways that underlie resistance to treatment in certain individuals but not others.
“These latest findings are an exciting step forward as they indicate an alternative treatment for a subset of patients who do not respond to current therapies as well as a basis for personalised targeting of medicines to treat this chronic inflammatory condition,” said Prof Powrie (pictured right), the Oxford BRC’s Theme Lead for Gastroenterology and Mucosal Immunity.
Consultant Gastroenterologist Professor Simon Travis of the TGU said: “As a specialist in treating ulcerative colitis and Crohn’s disease, it is hugely exciting to find tools that can help us to select the best possible treatment for each individual.
“This means that we will no longer be in the realm of trial and error, but able to precision-target treatment based on the dominant driver of inflammation in that person.”