PHD1 useful for pharmacologic inhibition in IBD: Research

Research into inflammatory bowel disease (IBD) led by UCD Conway Institute scientists with national and international collaborators has identified a key regulator involved in maintaining the functional integrity of the gut lining. The findings, published recently in the scientific journal, Gastroenterology, provide information that may be important in developing a new therapeutic approach to the treatment of the disease.

The underlying genetic or environmental causes of inflammatory bowel disease remain largely unknown. However, the major problem associated with this chronic condition is that the lining of the gut becomes leaky, allowing material from the lumen of the intestine to pass through this barrier and trigger an inflammatory response.

The intestinal barrier works by maintaining a delicate balance between the proliferation and death of epithelial cells at the surface of the barrier. If the balances tips so that more cells die than grow, as is the case in IBD, the barrier is no longer intact and cannot function properly.

This latest research led by Conway Fellow, Professor Cormac Taylor has shown that in the absence of an oxygen-sensing enzyme, prolyl hydroxylase 1 (PHD1), epithelial cell death is reduced and the intestinal barrier function is enhanced. Therefore, PHD1 may be a useful target for pharmacologic inhibition in IBD.

The team, which includes scientists from the University of Leuven, Belgium; University of Heidleberg, Germany; University College London and the Institute of Molecular Medicine, Trinity College Dublin,  propose that by delaying or suppressing epithelial cell death, the gut lining would be given time to heal and the integrity of the intestinal barrier could be restored.

Commenting on the research, Professor Taylor said "Inflammatory bowel disease is a condition in need of new and improved therapeutic options. Our current results indicate that targeting the PHD1 enzyme may represent one such approach."

In separate but related research, the Taylor group collaborate with the Irish biopharmaceutical development company, Sigmoid Pharma to facilitate targeted drug delivery to specific areas of the gut as part of a new therapeutic approach to the treatment of IBD.