General Information
The project METHYLOMIC is aiming to enhance the effectiveness of medication in chronic immune-mediated diseases such as Crohn’s Disease (CD), Rheumatoid Arthritis (RA), and Psoriasis (PsO). We aim specifically for the so-called biologicals, which are antibodies designed to target an inflammatory protein to reduce the inflammation.
Predictive biomarkers
Such biologicals have become a mainstay of therapy in common immune-mediated inflammatory diseases (IMID) including CD, RA, and PsO. Currently used biologicals target inflammatory proteins such as Tumor Necrosis Factor (adalimumab), leukocyte trafficking (vedolizumab), or IL-12/IL-23 (ustekinumab). However, IMIDs are complex diseases with a multifactorial background, so neutralizing one protein is often not enough to reduce the disease towards remission. If also differs from patient to patient. At present therefore, it cannot be predicted which biological will be effective in an individual patient, with only <40% of patients showing primary response to any given therapeutic. Treatment failure is associated with lasting disease course and disease complications, and increased health care costs. Hence the overwhelming need for predictive biomarkers to guide personalised medicine in IMID is evident, but no such predictive biomarkers is validated in clinical practice to date.
Better treatment response
While most efforts focused on genomic mutations, or gene expression, we took a different approach. In METHYLOMIC, we build on multiple previous cohort studies in which we confirmed epigenetic biomarkers (specifically DNA methylation) as the most stringent predictor of response to biological therapy, zooming in on CD. Specifically, we discovered and validated differential DNA methylation profiles in peripheral blood as biomarkers of response/deep remission for 3 approved biologicals in CD. Through the use of the state of the art in machine learning algorithms, treatment response could be predicted with up to 93% accuracy for each biological for CD, and RA.
Validation studies
METHYLOMICS is now committed to bringing personalised treatment-selection in CD and other IMID to clinical practice. We have teamed up clinical, epigenetic, and DNA diagnostics experts, patient organisations, and companies across 7 countries in Europe, for further validation studies. We will also develop a marketable rapid (2 weeks) targeted methylation assay that we then validate in a unique prospective randomised clinical trial for CD. Efficiency and cost-effectiveness is assessed in great detail and regulatory approval is guided by experts to assure delivery of the first epigenetic kit personalised treatment of CD.
