New research may pave the way for treatment that prevents intestinal scarring, strictures

Living with inflammatory bowel disease (IBD) presents many challenges. For some people, fibrosis of their gastrointestinal (GI) tract is one of the most significant. Fibrosis refers to a buildup of scar tissue. As this tissue accumulates, stricture, or narrowing of the intestines, can develop. Often, this makes endoscopic treatment or surgery necessary. But even with treatment, the strictures are likely to return. More surgeries may be needed. And that can lead to other complications and poor quality of life. It can also result in higher healthcare costs.

Chronic inflammation causes scarring. So, experts thought newer anti-inflammatory treatments developed in the last two decades might help reduce strictures in IBD patients. Unfortunately, that didn’t happen. But now there’s new hope for developing a treatment to prevent intestinal scarring. It comes thanks to research supported, in part, by a grant from the Crohn’s & Colitis Foundation Litwin IBD Pioneers initiative.

About the research: Fighting intestinal fibrosis

Currently, only two medications for fibrosis are approved by the Food and Drug Administration. These drugs are pirfenidone and nintedanib. Both address scarring in the lungs. There are no approved drugs for intestinal fibrosis.

Litwin IBD Pioneers awarded their grant to researchers who were trying to develop an antifibrotic medication for IBD. The researchers aimed for a drug they could deliver directly to a stricture site. And they hoped it could be a sustained-release medication. That’s a type of drug that prolongs the medication’s effects. In this case, researchers wanted to find a medication that could act throughout a patient’s intestinal healing process.

The researchers began by using a process known as high-throughput drug screening to look at more than 1,500 existing drugs. It allowed them to quickly zero in on small molecules with antifibrosis properties. The screening helped the researchers identify the drug sulconazole as having great potential for fighting fibrosis. It’s a topical medication. Normally, doctors use it to treat fungal infections.

Researchers formulated sulconazole into tiny, injectable nanocrystals (Sul-NC) that could gradually release the drug over time. They then tested the treatment in three animal models: mice with fibrosis of their bowels, mice with fibrosis of their skin, and pigs with strictures of their esophagus.

The researchers’ study showed that Sul-NC helped prevent fibrosis in the mice. It produced results that were as good or better than the drug pirfenidone, which they also tested.

In the pigs, Sul-NC prevented stricture formation. Researchers found the treatment was safe and well-tolerated with both the pigs and mice.

Why is this research important? The impact of fibrosis, strictures in IBD patients

There’s an urgent need to find a treatment that prevents GI fibrosis in IBD. Up to 54% of all Crohn’s disease patients will develop fibrosis-related strictures within 20 years of their diagnosis. Stricture risk also exists for ulcerative colitis patients, although to a lesser extent. Preventing these events could significantly improve patients’ health and overall well-being.

This is an early study. Results with animals don’t always translate to patient care. So, more research is needed before clinical trials in humans can take place. But researchers learned more about the actions of sulconazole. They also met their goals of developing a sustained-release medication and delivering the medication directly to the area of tissue damage.

These advances are noteworthy. Sustained-release drugs stay in the body longer than single-release medications. That’s important given that fibrosis worsens over a period of days or weeks. Drugs that clear the body too quickly simply may not work as well as sustained-release medications.

Direct delivery of the drugs to the site of scarring offers the potential to limit side effects. Adverse effects are more likely to occur when a drug travels through the entire body.

What’s important about the study for researchers is it offers a roadmap for the work ahead. Even more important, however, for IBD patients, the study offers hope for a life free of fibrosis and strictures.

The study appears in the journal Gastroenterology.

Litwin IBD Pioneers is made possible, in part, by generous support from the Swarzman and Pittelman families.