IBD: Medication may help treat symptoms of inflammatory bowel disease

Evan Walker
Evan Walker TheMediTary.Com |
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Scientists are studying treatments to reduce inflammation in Crohn’s disease and ulcerative colitis. Tom Werner/Getty Images
  • Inflammatory bowel disease is a term that includes Crohn’s disease and ulcerative colitis.
  • Researchers recently conducted a study of a new medication in mice with inflammatory bowel disease to see if the drug could suppress an enzyme that is up-regulated in this disease.
  • By the end of the study, the scientists say they were able to reduce inflammation in the colons of the mice.
  • While the medication needs further research and testing, experts say it has promise for being another treatment for people with inflammatory bowel disease.

Inflammatory bowel disease (IBD) affects the gastrointestinal tract by causing chronic inflammation, which contributes to pain, bloating, and other symptoms.

According to the Centers for Disease Control and Prevention (CDC), approximately 3 million adults in the United States have IBD, which includes Crohn’s disease and ulcerative colitis.

While there are treatments available for IBD, sometimes they may not work for people with severe forms of the condition.

This led researchers at the Johns Hopkins University School of Medicine in Maryland to try to create a new medication to help people get some relief from symptoms.

The researchers say they identified an enzyme that is over-expressed in people with IBD and wanted to develop a therapeutic that would lower levels of the enzyme.

In their study, the researchers said they were able to reduce inflammation and normalize the colon structure of the mice.

The study is published in the journal Science Translational Medicine.

IBD can be damaging to the body.

According to the CDC, ulcerative colitis can damage the rectum and the colon while Crohn’s disease can cause issues in “any part of the GI tract.”

“Inflammatory bowel disease is a problem where inflammation will cause injury to the lining of the intestine, the large bowel, the colon, and that injury can be progressive,” Dr. David Binion explained earlier this year during a UPMC HealthBeat podcast.

Binion is an IBD specialist and the co-director of the University of Pittsburgh Medical Center IBD Center.

“People can develop problems over time that might lead to hospitalization, surgeries,” Binion said. “It can be a fairly serious issue if left untreated and unaddressed.”

Some treatments for IBD include biologic drugs and corticosteroids. However, these treatments may not help a significant percentage of people with IBD.

According to the study authors, “There is an urgent need to develop therapeutics for inflammatory bowel disease because up to 40% of patients with moderate-to-severe IBD are not adequately controlled with existing drugs.”

In their efforts to find treatments that can help people with more severe symptoms, the researchers identified the enzyme glutamate carboxypeptidase II, which they referred to as GCPII in the study.

The authors note that GCPII is not typically found in the colon or Health">ileum (the final part of the small intestine), but that the enzyme was up-regulated in samples taken from people with IBD. As such, they decided that creating a treatment to target GCPII would be worth testing.

From there, they reviewed several GCPII inhibitors and decided to test the compound (S)-IBD3540 in mice with IBD to see whether they could suppress GCPII and improve symptoms.

The scientists administered the inhibitor to the mice orally on a daily basis for a period of 6 weeks.

After giving the (S)-IBD3540 oral inhibitor to the mice for 6 weeks, the researchers assessed fecal matter from the rodents as well as tissue samples after euthanizing the mice.

With the fecal matter, the scientists noticed that the consistency of the stools was improved with less diarrhea, which they say indicated anti-colitis activity from the (S)-IBD3540 inhibitor. They also noted less blood in the stool samples, indicating a decrease in rectal bleeding compared to samples taken before giving the mice the medication.

When testing the tissue samples, the study authors said the treatment improved inflammation in the colon. They said that they detected reduced levels of colon pro-inflammatory cytokines.

The (S)-IBD3540 inhibitor also improved the structure of the colon. The authors said the data “provided direct evidence linking GCPII enzymatic activity to colon epithelial barrier structure and function.”

Another benefit the researchers said occurred is that higher doses of (S)-IBD3540 led to a 75% inhibition of colon GCPII activity in mice with dextran sodium sulfate-induced colitis.

The researchers also conducted an experiment using (S)-IBD3540 with human colon epithelial air-liquid interface monolayers. They found that (S)-IBD3540 “protected against submersion-induced oxidative stress injury by decreasing barrier permeability, normalizing tight junction protein expression, and reducing procaspase-3 activation.”

The scientists noted that work is under way to begin the first human trials with (S)-IBD3540.

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