New research undertaken at Sanford Burnham Prebys Medical Discovery Institute has disclosed a new therapeutic target for the treatment of inflammatory bowel disease (IBD). The findings also identifieda protein called "protein kinase C" that shows promise as a biomarker of IBD severity. Researchers focused on Paneth cells in the intestine which secrete antimicrobial peptides that forestall inflammation. By inhibiting a protein called EZH2, the team found that Paneth cell loss could be prevented. The extent of Paneth cell loss can also be marked by the amount of protein kinase C presents which decreases as IBD gets worse. The findings are published in this month's Cell Reports.
IBD includes conditions such as Crohn’s disease and ulcerative colitis, and impacts some 1.4 million Americans. Current treatments address the symptoms, including pain and unpredictable diarrhea, but not the disease itself IBD increases the risk of intestinal cancer by up to 60% , and 70% of patients with Crohn’s disease eventually have surgery. The study used an in vitro model to demonstrate that overactive EZH2 turns off genes needed to generate the protective Paneth cells. Blocking EZH2 helped to restore normal levels of the cells, suggesting that EZH2 inhibition could be an effective target for new IBD therapies. The study authors noted that EZH2 inhibitors are already in development for the treatment of other cancers, and that these could be tested for effectiveness against IBD relatively soon. Read a news story about the discovery here. The article abstract may be read here.