Significant step towards personalised treatments for IBD
Inflammatory bowel disease (IBD) – the chronic inflammation of the entire digestive system – affects approximately 2 to 3 million people in Europe alone and causes significant discomfort and suffering. The condition is typically diagnosed through an examination of a patient’s history, routine blood tests in order to find non-specific inflammatory biomarkers and invasive procedures that can sometimes prove unnecessary. Another key issue is the fact that up until now, medical professionals have been unable to accurately offer prognoses based on biomarkers alone. ‘The best available tool at the moment – a faecal marker – is sensitive at picking up inflammation, but it does not differentiate between Crohn’s disease and colitis,’ explains IBD BIOM project coordinator Professor Jack Satsangi, Chair of Gastroenterology at the University of Edinburgh, UK. ‘It is a good screening tool, but does not obviate the need for colonoscopy and radiology; it just reduces unnecessary ones in people who don’t have inflammation. Faecal markers are also more problematic in terms of acceptability to the patients involved. ’ Road to personalised treatments Through combining a large number of previously bio-banked samples with data from new patients at the point of diagnosis, the IBD BIOM project has been able to identify genome-wide changes in DNA methylation associated with an altered gene expression at different stages of IBD. This opens the door to identifying new biomarkers that can provide insights into disease pathogenesis. ‘Our aim in this project was to develop non-invasive ways of finding more sensitive biomarkers,’ says Satsangi. ‘Over the next decade I predict that we’ll see a move towards identifying biomarkers that enable medical professionals to stratify patients in terms of how their diseases behave. This means that more aggressive forms of the disease can be singled out for the early use of surgery or new biological therapies for example, while less aggressive forms of the disease can be observed without intensification of treatment .’ This project is therefore keeping European medical research ahead of the curve when it comes to personalised medicine. ‘There are a whole host of new therapies and biological agents that could be used to treat IBD,’ says Satsangi. ‘The challenge for us is to find the biomarkers that predict response to a particular therapy. There are specific therapies that fit the right profile.’ Game changing discoveries A key strength of the IBD BIOM project was its ability to access a large number of samples from previous projects and to follow new patients from the point of diagnosis. From this strong pool of data, the project team was able to look at epigenetic alterations associated with IBD and defined the disease – associated methylome – the complete overview of nucleic acid methylation modifications in an organism's genome – for the first time. ‘This is a game changer,’ says Satsangi. ‘Beforehand, people were not even sure if we could find reproducible epigenetic alterations associated with IBD. Not only were we able to find these; we were able to demonstrate that they reflect the degree of inflammation in patients, and the progression of the disease. This is a big finding.’ Another significant project achievement has been the development of activomics, a novel technology established by one of the IBD-BIOM partners for biomarker discovery. Activomics analyses the enzymes responsible for post-translational modifications (phosphorylation, glycosylation or proteolysis). The hope now is that the project findings will be used to further develop personalised care for IBD, and that new targets for targeted drug therapies might be found.
Keywords
IBD BIOM, IBD, digestive, Crohn’s, colitis, activomics, methylome, biomarkers, DNA, blood, bowel
