Norovirus Research Findings May Point to New Crohn’s Disease Treatments

At least half of all Americans have a genetic mutation that makes the cells lining their gut more vulnerable to damage. So why doesn't half of America have Crohn's disease?

Researchers at NYU Langone, funded in part by the Crohn's & Colitis Foundation, sought to answer this question by studying a person’s likelihood of developing inflammatory bowel disease (IBD), and their findings have uncovered a potential new target for treating Crohn’s disease.

Most people who have Crohn’s disease have a mutation that makes their gut lining more vulnerable to damage, but puzzlingly, Crohn’s patients share this mutation with at least half of the American population. The NYU Langone researchers believe that most people with the mutation do not go on to develop IBD because immune defender cells (also known as T-cells) in healthy people secrete a protein called apoptosis inhibitor 5 (API5). API5 sends a signal to the immune system to stop attacking the gut lining cells, keeping their gut tissue healthy and inflammation-free.

That is until this person contracts norovirus, commonly known as a stomach bug. When the researchers observed mice bred to have a rodent form of Crohn’s disease, the T-cells of the mice infected with norovirus were unable to secrete API5, and the cells lining their guts were killed. 

Researchers separated mice bred to have the same genetic mutation seen in humans into two groups: one treated with an injection of API5, and one untreated. All of the mice that received an API5 injection survived, and half of the untreated group died.

Researchers then constructed “mini guts” from human tissue; specifically, humans who tested positive for the genetic mutation predisposing the cells that line their gut to damage. They found that dropping API5 into these structures made out of only gut lining cells protected the cells from damage.

Adding API5-producing T-cells to the “mini guts” also protected the gut lining cells from damage; researchers found that people with Crohn’s disease naturally have between 5-fold and 10-fold fewer API5-producing T-cells than people without IBD.

These findings about API5 could open up pathways to new ways to treat Crohn’s disease. A new treatment that specifically targets API5 could become an option in the future, but the safety of administering API5 injections in humans remains unclear. Researchers hope to further study the long-term safety and efficacy of API5 injections to gain a better understanding of API5 as a potential new treatment option.