Scientists say they have made a ‘holy grail’ breakthrough after discovering a major cause of inflammatory bowel disease (IBD) that could unlock new treatments.
Until now, experts were unsure what exactly triggers the condition, which includes Crohn’s disease and ulcerative colitis.
But researchers in London have discovered a genetic weakness present in 95 per cent of people with IBD.
And in what could be good news for the half a million Brits with the condition, they found already existing medications — prescribed for other conditions — could combat this weakness.
Experts said the discovery could help sufferers get targeted treatments quicker and even help other patients with other immune-based disorders affecting the spine, liver and arteries.
Dr James Lee, an expert in genetic mechanisms of disease at the Francis Crick Institute in London who led the research, said: ‘What we have found is one of the very central pathways that goes wrong when people get inflammatory bowel disease and this has been something of a holy grail.’
‘Even for pure, fundamental immunology this is a really exciting discovery.
‘But to show this is dysregulated in people who get disease not only gives us a better understanding of the disease, it tells us this is something we can treat.’
More than 10million people globally are thought to be affected by IBD.
Existing treatments don’t work for every patient and an incomplete understanding of what causes IBD in the first place has hindered the hunt for new ones.
IBD arises when the immune system mistakenly attacks the bowel, causing an array of debilitating symptoms including abdominal pain, diarrhoea and blood in stools.
The disease can also cause sudden weight loss and crippling fatigue.
While no cure is available, symptoms can be managed with drugs. These tend to be most effective when given soon after diagnosis.
However, for some patients these medications don’t work and they can need to undergo major surgery.
For example, a fifth of people with Crohn’s will need surgery in the first five years after their diagnosis.
Researchers of the new study, which also featured experts from University College London and Imperial College London focused on a so-called ‘gene desert’ — an area of human DNA that doesn’t code for proteins.
But they found it contained DNA only seen in a type of white blood cell, which form part of the body’s immune system, called macrophages.
This boosted levels of a gene called ETS2 which is known to increase the risk of a person having IBD.
While no drugs specifically target ETS2, the authors, writing in the journal Nature, said existing medications prescribed for other conditions could be effective.
They highlighted a type of cancer drug called MEK inhibitors, which work by blocking specific proteins from growing, as a potential candidate.
And tests, conducted by the researchers, found MEK inhibitors not only reduced inflammation in the immune cells themselves but also in gut cell samples from patients with IBD.
However, as MEK inhibitors can negatively effect other organs, the researchers are now trying to find ways to deliver the drugs directly to patients’ macrophages.
They aim to start clinical trials within five years.
Christina Stankey, PhD student at the Francis Crick Institute, and study co-author, 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.’
Meanwhile, Ruth Wakeman, director of services at Crohn’s and Colitis UK said: ‘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.
‘This research is a really exciting step towards the possibility of a world free from Crohn’s and colitis.’
