Researchers have found, for the first time, that damage to the lining of the gut plays a key role in disease by making it leaky.
This allows bacteria to cross the gut lining into the body, intensifying inflammation in the stomach and the joints.
And the researchers have identified existing stomach-repairing drugs used for the digestive disorders, coeliac disease and Crohn’s disease that could be used treat rheumatoid arthritis, which affects about 400,000 people in the UK – a third of whom gain very little benefit from current therapies.
Laboratory tests on human tissue and mice samples found a drug currently in clinical trials for Coeliac disease – known as AT1001 – was effective at mending the gut and relieving symptoms while vercirnon, a treatment already being used on the NHS to treat Crohn’s is another potential candidate.
The researchers are now working towards a clinical trial involving one or more of these drugs in humans for rheumatoid arthritis.
“Our findings are exciting. They suggest that the stomach lining is a therapeutic target. Importantly, we found that using existing drugs that restore the gut-barrier integrity, could reduce the severity of arthritis,” says Professor Claudia Mauri, of University College London.
In a best case scenario, an existing drug will be found to be effective and become available for rheumatoid arthritis patients on the NHS within three to four years, Prof Mauri said – while stressing that it could be much longer and may never happen.
Experts not involved in the study said the findings significantly increase our understanding of disease that could lead to effective new treatments.
“This is an exciting study [that] may help to identify new ways to treat arthritis in some patients,” said Professor Simon Milling, of the University of Glasgow who edits the British Society for Immunology’s journal Immunology.
The study is published in the journal Med and was funded by the Versus Arthritis charity and government bodies UK Research and Innovation and the Medical Research Council.
Dr Neha Issar-Brown, Director of Research at Versus Arthritis said: “The findings are exciting on many fronts. Not only do they demonstrate a link between damage to the gut lining, its microbiome and rheumatoid arthritis, but they also show how it might be triggering the immune system and contributing to inflammation and the onset of RA. This research is truly impactful in opening new avenues for exploration.”
“This new research looks promising but it is still very early days,” added Arthritis Action’s medical advisor Wendy Holden.
The researchers found that, compared to healthy people, gut damage was greater even at the earliest stages of arthritis, and that the damage got higher the more the disease progressed. They were also surprised to find distinct signs of inflammation.
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