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Researchers discover major cause of inflammatory
bowel disease
London [UK], June 5 (ANI): Researchers have identified a new biochemical pathway
that is a major cause of inflammatory bowel disease (IBD) and related disorders
that can be addressed with existing medications. An autoimmune disease, such as
IBD, which encompasses Crohn’s disease and ulcerative colitis, presently affects
approximately 5% of the world’s population and one […]
ANI
05 June, 2024 11:17 pm IST
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London [UK], June 5 (ANI): Researchers have identified a new biochemical pathway
that is a major cause of inflammatory bowel disease (IBD) and related disorders that
can be addressed with existing medications.
An autoimmune disease, such as IBD, which encompasses Crohn’s disease and
ulcerative colitis, presently affects approximately 5% of the world’s population and one
in every 10 people in the United Kingdom1. These diseases are also becoming
increasingly widespread, with over half a million individuals in the UK living with IBD
by 2022, nearly double the previous prediction of 300,000.
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Despite increasing prevalence, current treatments do not work in every patient and
attempts to develop new drugs often fail due to our incomplete understanding of what
causes IBD.
Researchers done by Francis Crick Institute, in collaboration with UCL and Imperial
College London and their findings published in Nature, scientists at the Crick
journeyed into a ‘gene desert’ – an area of DNA that doesn’t code for proteins – which
has previously been linked to IBD and several other autoimmune diseases.
They found that this gene desert contains an ‘enhancer’, a section of DNA that is like a
volume dial for nearby genes, able to crank up the amount of proteins they make. The
team discovered that this particular enhancer was only active in macrophages, a type
of immune cell known to be important in IBD, and boosted a gene called ETS2, with
higher levels correlating with a higher risk of disease.
Using genetic editing, the scientists showed that ETS2 was essential for almost all
inflammatory functions in macrophages, including several that directly contribute to
tissue damage in IBD. Strikingly, simply increasing the amount of ETS2 in resting
macrophages turned them into inflammatory cells that closely resembled those from
IBD patients.
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The team also discovered that many other genes previously linked to IBD are part of
the ETS2 pathway, providing further evidence that it is a major cause of IBD.
Specific drugs that block ETS2 don’t exist, so the team searched for drugs that might
indirectly reduce its activity. They found that MEK inhibitors, drugs already prescribed
for other non-inflammatory conditions, were predicted to switch off the inflammatory
effects of ETS2.
The researchers then put this to the test, and discovered that these drugs not only
reduced inflammation in macrophages, but also in gut samples from patients with IBD.
As MEK inhibitors can have side effects in other organs, the researchers are now
working with LifeArc to find ways to deliver MEK inhibitors directly to macrophages.
James Lee, Group Leader of the Genetic Mechanisms of Disease Laboratory at the Crick,
and Consultant Gastroenterologist at the Royal Free Hospital and UCL, who led the
research, said: “IBD usually develops in young people and can cause severe symptoms
that disrupt education, relationships, family life and employment. Better treatments
are urgently needed.
“Using genetics as a starting point, we’ve uncovered a pathway that appears to play a
major role in IBD and other inflammatory diseases. Excitingly, we’ve shown that this
can be targeted therapeutically, and we’re now working on how to ensure this approach
is safe and effective for treating people in the future.”
Christina Stankey, PhD student at the Crick, and first author along with Christophe
Bourges and Lea-Maxie Haag, said: “IBD and other autoimmune conditions are really
complex, with multiple genetic and environmental risk factors, so to find one of the
central pathways, and show how this can be switched off with an existing drug, is a
massive step forwards.”
Volunteer participants from the NIHR BioResource, with and without IBD, provided
☰ samples that contributed to this research. The research was funded by Crohn’s
blood
and Colitis UK, the Wellcome Trust, MRC and Cancer Research UK, and the researchers
worked with collaborators across the UK and Europe.
Ruth Wakeman, Director of Services, Advocacy and Evidence at Crohn’s & Colitis UK
said: “Every year, more than 25,000 people are told that they have Inflammatory Bowel
Disease. Crohn’s and Colitis are complex, lifelong conditions for which there is no cure,
but research like this is helping us to answer some of the big questions about what
causes them. The more we can understand about Inflammatory Bowel Disease, the
more likely we are to be able to help patients live well with these conditions. This
research is a really exciting step towards the possibility of a world free from Crohn’s
and Colitis one day.”
Lauren Golightly is 27 years old and was diagnosed with Crohn’s Disease in 2018 after
experiencing stomach cramps, blood in her poo and irregular bowel habits.
She said: “Crohn’s has had a huge impact on my life. I’ve had a rocky road since
diagnosis, with many hospital admissions, several different medications and even
surgery to have a temporary stoma bag. One of the hardest things about having
Inflammatory Bowel Disease ( IBD) is the uncertainty around it. I still experience flare-
ups and can still spend quite a bit of time in hospital. Learning about this research is so
exciting and encouraging. I am hopeful this could potentially make a difference for
myself and so many other hundreds of thousands of people living with IBD.” (ANI)
This report is auto-generated from ANI news service. ThePrint holds no responsibility
for its content.
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