The development of predictive epigenetic biomarkers to guide successful treatment of Crohn’s Disease

The development of predictive epigenetic biomarkers to guide successful IBD treatment

Project Overview. We are developing biomarkers to predict successful treatment of Crohn's disease. GenDX, Health Holland, and Amsterdam UMC have joined forces to develop a rapid method based on epigenetic biomarkers in blood samples to match the most suitable medication to the right patient.

Impact and Relevance. Crohn's disease is a chronic inflammatory bowel disorder without cure. More than 1 million people in Europe and North America suffer from it. Biological drugs such as anti-TNF antibodies have improved care for patients, but only 30 to 70% respond fully to treatment. Currently, predicting response is impossible, leading to prolonged searches for effective treatments.

Approach and Innovation in this Project. Our approach utilizes cutting-edge AI technology to detect small epigenetic markers in blood. We use technology that can measure 850,000 markers at once, but we also develop a quick test for targeted testing. The markers vary among individuals and are compared to earlier blood samples measured in 360 patients whose response to medication was known. By detecting biomarkers before therapy begins, we can predict therapeutic response and support the doctor's choice of medication.

Project Implementation. In the project, we strictly select patients suitable based on their disease course follow up and we will document their response to various types of medications through endoscopy and symptom scores. The results will lead to a web-based biomarker dashboard for worldwide optimization of CD patient treatments in hospitals.

Deliverables and end results. The project has delivered 3 research papers, a patent on epigenetic biomarkers, and 2 conference proceeding. Ishtu Hageman has delivered a PhD thesis on the topic in 2023. The end results comprise a proof of principle of the technology and the current project is followed up by a large scale prospective clinical trial (n=372 patients) that aims to provide clinical utility of the developed test (www.methylomic.eu).

Summary

Some 60,000 patients suffer from IBD in the Netherlands, over 1 million residents in the USA and 2.5 million in Europe are estimated to have IBD, and the incidence in especially Asian countries is rising dramatically. Current standard care using various biological medications in IBD patients has important shortcomings, which include (1) significant side-effects such as infections, lymphomas, and skin cancer, (2) loss of response to treatment over time in 23-46% of patients that brings a need to escalate treatment, including surgical interventions, and (3) high economic costs of chronic treatment. There is thus a strong need for a means to guide optimal therapy to patients on the basis of their personal needs, which will lead to sustained clinical response for IBD patients. In this project, we aim to identify epigenetic DNA marks that distinguish therapy responsive patients from those that no not respond to therapy, to guide the right treatment to treatment-sensitive patients. Further, we aim to study those epigenetic marks that characteristic treatment resistant patients, to understand the disease course, to come to a new way of treatment in patients resistant to current medication.

Technology Readiness Level (TRL)

- 3 -

Time period

42 months

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