Towards personalised therapy in stricturing crohn's disease- exploring and exploiting the role of NADPH oxidase in intestinal fibrosis

Crohn's disease, a member of the family of inflammatory bowel diseases, causes inflammation throughout the digestive tract and frequently results in fibrosis (scarring) of the intestine, which will cause narrowing and ultimately bowel obstruction. Available treatments can dampen the inflammation, but do not prevent fibrosis. It is currently impossible to predict which patients will develop fibrosis and there are no medicines to prevent or treat it. Patients who develop fibrotic strictures need surgery to remove the blockage, often several times, with significant impact on their quality of life. The incidence of Crohns disease in Irish children has doubled since 2005 with 30%-50% of patients developing intestinal fibrosis. Therefore, there is a large patient need for a tool (a biomarker) to predict which patients are at risk of developing fibrosis and to find drugs to treat it. The goal of this study is prediction and early treatment of fibrosis. We have some understanding of the processes involved in fibrosis in the lung, kidney and liver, but intestinal fibrosis is poorly understood. A new molecule involved in promoting lung fibrosis is the oxidant-generating enzyme NADPH oxidase. Recognition of the importance of this enzyme has triggered an international drive towards developing drugs targeting its activity. In this project we will establish whether this enzyme plays a key role in intestinal fibrosis by examining fibrotic tissue from patients with Crohn’s disease and we will explore its potential to serve as a new biomarker. We will perform pre-clinical testing of enzyme inhibitors which are currently in early-phase trials or in development, to determine whether they may represent a new treatment option for intestinal fibrosis. This project has the potential to directly improve disease management and quality of life in patients with Crohns disease by providing a new and individualised treatment.

Award Date: 26 May 2016
Award Value: €259104
Principal Investigator: Professor Emily Stenke
Host Institution: University College Dublin
Scheme: Research Training Fellowships for Healthcare Professionals