There may be hope for people who suffer from inflammatory bowel disease (BDS). British scientists from the the Francis Crick Institute, working with UCL and Imperial College London, said they have discovered a new biological pathway that is a principal driver of IBD and related conditions, and which can be targeted using existing drugs. This could lead to a cure.
Researchers at the Crick Institute delved into a previously puzzling area of DNA linked to IBD and other autoimmune diseases. This region, nicknamed a “gene desert” because it lacks protein-coding genes, held a surprise. They discovered an “enhancer” within this desert. Imagine an enhancer like a volume knob for nearby genes, controlling how much protein they produce. Interestingly, this specific enhancer was only active in macrophages, immune cells crucial in IBD. It boosted a gene called ETS2, and higher levels of ETS2 correlated with a greater risk of developing the disease.
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“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,” said 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.”
Inflammatory bowel disease (IBD) is an umbrella term used to describe chronic inflammatory conditions of the gastrointestinal (GI) tract. The two main forms of IBD are ulcerative colitis and Crohn’s disease.
In IBD, the immune system mistakenly attacks the healthy tissues in your GI tract, causing inflammation. This inflammation can lead to a variety of symptoms, including diarrhea, abdominal pain and cramping, urgent need to have a bowel movement (urgency), rectal bleeding, weight loss and fatigue.
The exact cause of IBD is unknown, but it is thought to be a combination of genetic and environmental factors. There is no cure for IBD, but there are treatments that can help control the inflammation and symptoms.
“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,” said Christina Stankey, PhD student at the Crick, and first author.
About 5% of the world’s population, and one in ten people in the UK, are currently affected by an autoimmune disease, such as IBD, the umbrella term for Crohn’s disease and ulcerative colitis. These diseases are also becoming more common, with over half a million people living with IBD in the UK as of 2022, nearly double the 300,000 previously estimated.
“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,” said the scientists.
