Finding ways to stop fibrosis in Crohn’s

2018

2018


By understanding the mechanisms that drive fibrosis we will be able identify targets for future therapies.

Prof Andrew Silver
Barts and the London School of Medicine

What is this research looking at? 

The chronic inflammation associated with Crohn’s Disease can cause tissue damage and scar tissue to develop in the bowel in a process called fibrosis.  This can cause a stricture (narrowing) of the bowel, which can lead to blockage.  About one-third of people with Crohn’s will develop strictures, and may experience symptoms such as pain and vomiting due to an obstruction.  No current treatment can reverse or cure fibrosis, and strictures caused by fibrosis are the main reason for surgery in people with Crohn’s.  Financial costs related to surgery make up one-fifth of the costs associated with the management of Crohn’s.  Surgery is also associated with a higher risk of unemployment, and poorer quality of life due to disease recurrence.  Therefore, alternative treatments are needed to prevent or reverse fibrosis in Crohn’s. 

Intestinal fibrosis is a complicated process that is not fully understood.  It involves cells in the bowel wall called fibroblasts.  Fibroblasts make collagen – a protein that encourages fibrosis and causes strictures in people with Crohn’s.  Understanding how fibrosis and bowel obstruction happens in Crohn’s will improve the likelihood of discovering new treatments.  The researchers will investigate an important chemical change in fibroblasts from people with Crohn’s.  When this change goes wrong in other diseases, it causes inflammation and fibrosis, which can be treated using drugs.   

The researchers have already shown that valproic acid – already used for other conditions such as epilepsy – has an effect on this chemical change, and stops the formation of collagen.  Testing whether valproic acid drugs that have already been approved for some uses can be used to treat fibrosis in Crohn’s could provide a cheaper and faster route to treatment than the discovery of new drugs.  Researchers need to understand how valproic acid works, and how certain processes in the body control the effect of valproic acid on the production of collagen.  First researchers will use gut tissue from people with Crohn’s to understand how this drug acts, in particular how it inhibits a protein involved in collagen production during fibrosis. They will determine whether blocking this protein can be used as a targeted treatment of fibrosis in the bowel.  Drugs that prevent, delay or reverse fibrosis will have a major impact on people’s quality of life and ability to work.  

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

Researchers hope that valproic acid, or similar drugs can be used as new treatments for fibrosis in Crohn’s. There are currently no specific treatments that prevent or reverse fibrosis in the bowel of people with Crohn’s, therefore this would be a major advancement to improve quality of life and reduce the cost of disease management.     

Who is leading this research:  Professors Andrew Silver and James Lindsay, Blizard Institute, Barts and The London School of Medicine & Dentistry 
Our Funding: £73,573 
Duration: 12 months 
Official title of application: Restoration of histone acetylation levels and reduction of collagen expression via inhibition of HIC-5: a new strategy to limit fibrosis in Crohn’s Disease