For many affected by Inflammatory Bowel Disease (IBD) a world where your genes could predict how your IBD will behave – so the best treatment can be started from the point of diagnosis would be life-changing. A new clinical trial will be putting this exciting research to the test.
Dr James Lee (pictured above) is a consultant gastroenterologist and Wellcome Trust Intermediate Clinical Fellow at the University of Cambridge and Harvard University.
In 2008, Crohn’s and Colitis UK awarded a £81,981 grant that enabled James and his team to complete a three-year study titled Gene Expression Profiling in Crohn’s Disease and Ulcerative Colitis.
The research aimed to ascertain whether there were certain genes in patients that could make the diseases behave differently. This could then help develop a test that could predict disease severity.
This important research led to the identification of a gene signature that could predict disease progression and identify the likelihood of an increase in severity.
Building on this research, the charity awarded a second grant of £107,680 to James and the team for a follow-up study. The Genetics of Prognosis in Crohn’s Disease aimed to determine why such differences in disease behaviour occur in the first place.
This successfully identified several genetic risk factors that alter the course of Crohn’s Disease, and which are now being investigated to develop better treatments.
“The first study was very successful,” says James, explaining that it involved them identifying a “gene signature” among a subset of white blood cells.
“If you had looked for that in a blood sample from a patient, you probably wouldn’t have found it as all the white blood cells would be mixed in together,” he adds.
The team has spent a number of years trying to find a “surrogate” for the gene signature that can be detected in whole blood, and James hopes the new trial will lead to personalised IBD treatments which would tell them the same information.
“That’s something we have now done and we’re going to be using that biomarker in a nationwide trial” says James. “Using the biomarker we will be able to do a test at the point of diagnosis that will tell us if a person is likely to run an aggressive course of Crohn’s. We can therefore introduce a much stronger treatment from the start, to prevent months, possibly years, of the disease failing to respond to weaker treatments while symptoms gradually ramp up.
"We also want to identify patients who can be managed with fairly mild treatments to prevent them experiencing unnecessary side effects from medications that might be considered simply because they have Crohn’s.”
We couldn’t have done this research without the funding support from Crohn’s and Colitis UK, no one had really looked to see if there was a genetic contribution to severity before and the charity took a risk on funding both these studies. If this trial is successful, it could revolutionise how we treat IBD.
Dr James Lee
Cambridge Institute for Medical Research
The trial will be carried out with newly diagnosed patients in 50 NHS hospitals across the UK. The recruitment period will run for two years and patients who participate in the trial will be tested to predict their likely disease behaviour and given the most appropriate treatment based on their results.
They will then be monitored for a year, after which doctors will assess whether personalising their treatment has led to an improved outcome. The trial is funded by the Wellcome Trust.
“Ultimately, I want to move towards personalised treatments.” Says James. “If we can change it so that your IBD - which could be very aggressive - becomes mild and does not have much of an impact on your life, that could make such a difference. We don’t have a cure but we can improve how it is treated.”
This article was originally published in full in our Connect magazine (Autumn 2017).To receive future editions of the magazine and to enjoy other benefits become a member today.
