Recently, researchers from Amsterdam UMC and other European hospitals, together with several companies and patient organizations, have proposed a revolutionary
strategy for the treatment of Crohn's disease and received funding of more than
€10 million. The research involves the selection of treatments based on the DNA
"methylome," which is of critical importance to the many Crohn's disease patients who suffer from chronic intestinal inflammation and symptoms such as diarrhea, abdominal pain and weight loss. Led by AGEM Professors Geert D'Haens and Wouter de Jonge, the research is funded by a prestigious European Union (Horizon Europe) grant.

Discovery from Amsterdam UMC and Oxford

Significant progress is in sight for the treatment of Crohn's disease. Indeed, researchers at Amsterdam UMC and colleagues in Oxford have discovered that certain elements are present on a patient's DNA (so-called methylation markers) that can predict whether a patient will respond to a particular treatment. This is of great importance because the majority (more than 60%) of patients with Crohn's disease do not respond well to available modern treatments (so-called biologicals). Moreover, it is currently impossible to predict which treatment will be most effective to control the disease. This leads to incomplete treatment of the disease, allowing the disease to flare up in patients, as well as complications that often require surgery, which is a disease burden for the patient and also leads to high societal costs. Therefore, there is a need to focus treatments more on individual patients and be able to predict which treatment they will respond best to, also known as "personalized medicine."

Seeking for a solution

The researchers will now work with several companies and patient organizations to develop a rapid test and demonstrate in a clinical trial of 400 patients with Crohn's disease, that the test works in clinical practise. Based on methylation markers in a patient's blood, it will be determined which treatment will work best for that patient (see also image below created with Biorender.com) and that therapy will then be started. For comparison, a group of identical patients will be treated in the normal way without using the test. This will help determine whether the test leads to more effective treatments. Similar data will also be collected from patients with rheumatoid arthritis or the skin disease psoriasis so that the test can be developed for these patient groups in the future.

Kick-off

The study, called METHYLOMIC, will start in January 2023 in a large number of European and English hospitals and will last 4 years. The validation of this test would be a great leap forward for patients with Crohn's disease and, in the future, other inflammatory diseases.