IBD therapy redesigned From established therapeutic regimens to prospective epigenetic approaches

Ulcerative colitis (UC) and Crohn’s disease (CD) are the two main entities in the spectrum of inflammatory bowel diseases (IBD) and cause a significant disease and financial burden. In recent decades the medical industry has gained much experience treating these diseases, however, no single suitable therapy exists for every patient. Within this heterogeneous patient group are multiple, as yet unidentified subgroups.
This thesis first compares validated remission-induction treatments for UC: ciclosporin and the more recently developed infliximab. While infliximab is many times more expensive than ciclosporin, research shows there is no difference between these therapies in terms of short- and long-term colectomy and acute exacerbation rates.
Secondly, epigenetic mechanisms of CD are explored. Epigenetic processes such as DNA methylation dictate which genes are active or dormant within each cell, and thereby also their behaviour. We describe methylation profiles of cells that contribute to the inflammatory and fibrotic complications seen in CD. One chapter elaborates on how the disease burden in colitic mice is clearly ameliorated when a specific micro-RNA, inhibiting translation of many genes, is blocked by a custom-designed anti-microRNA.
With recent technological advances it has become easier to broadly explore different physio-pathological systems in order to link and analyse the additive value to a disease. In this way, subgroups of patients are more easily identified and specific medication can be designed, leading to increased safety through fewer side effects and much higher efficacy rates.