Understanding what causes strictures

2014

Identifying the key processes that cause scarring in the gut.

2014


Our research is currently focused on the therapeutic potential of altering the genetic signalling pathway to prevent fibrosis in Crohn's disease

Prof Andrew Silver, Barts and the London School of Medicine

What the research is looking at:

Gut inflammation in Crohn’s Disease can result in the development of scar tissue - this is called fibrosis. Fibrosis involves a type of cell called a fibroplast multiplying and producing a protein called collagen. This collagen builds up to form strictures (narrowings) in the small intestine. Blockages caused by these strictures are a very common reason for surgery in Crohn’s Disease.

As yet, there is no medical therapy available to reverse fibrosis. However, researchers have already identified a particular chain of molecules called MicroRNAs (miRNAs) that may be linked with fibrosis. It is thought that these particular miRNAs may have an impact on a genetic pathway within the cell called ‘Wnt’. A genetic pathway is the chain of processes leading from a gene to creation of proteins or other molecules. It is already known that activation of the Wnt pathway is a common feature in a number of other diseases, including cancer and fibrosis of other organs. The researchers want to find out the role of this pathway in Crohn’s Disease, and whether modulating (altering) it may be a way of preventing or delaying fibrosis in Crohn’s Disease

Conclusions: The researchers were able to confirm their hypotheses. Firstly, they were able to show that the miRNAs are increased during fibrosis. Secondly, they were able to show that blocking the Wnt pathway in cells from the intestine could prevent fibrosis. These results suggest that blocking the miRNAs and the Wnt pathway (either alone or in combination) could be a novel treatment approach for reducing strictures in Crohn’s Disease.

What do researchers think this could this mean for people with IBD?

If researchers are able to identify the chain of genetic and molecular processes that lead to fibrosis, then particular treatments and drug combinations could be used to inhibit those processes. This could reduce the formation of strictures and the associated need for surgery in patients with Crohn’s Disease.

Who's leading the research: Prof Andrew Silver, Dr James Lindsay, Barts and the London School of Medicine

Our funding: £73,134 over 12 months

Official title of the application: “Inhibition of Wnt signalling using small molecule inhibitors and C14MC antagomiRs as a novel combination therapy for fibrostenosing disease in Crohn’s disease.”

Tags: Genetics / Strictures