Researchers Look Beyond Inflammation for New Therapeutic Targets
Researchers from Washington University School of Medicine report that they have isolated a possible new target for the treatment of inflammatory bowel diseases (IBD) including Crohn’s disease and ulcerative colitis. Existing therapies for IBD focus on the patient’s overactive immune system and its role in provoking inflammation using biologic drugs called TNF blockers. But for many patients these treatments are not effective in providing relief from the abdominal pain, rectal bleeding, and diarrhea that accompany their IBD. Working with mouse models, the team identified a gene called SERPINE-1 and associated protein that is present at high levels in the gut of animals with induced inflammation similar to IBD. Senior author Thaddeus Stappenbeck, MD, PhD, commented, “There’s a lot of interest in novel therapeutic approaches for IBD because inhibiting inflammatory molecules doesn’t work for all patients. We found a unique target that’s not an inflammatory molecule, and yet blocking it reduces inflammation and signs of disease, at least in mice.” The findings were published last week in the journal Science Translational Medicine.
The research team compared levels of the SERPINE-1 gene in mice with induced IBD to a group treated with a harmless chemical and found that the gene was expressed at a level 6 times higher in the IBD group. But when a subset of these mice was treated with a compound that tamps down the activity of the gene, they exhibited less intestinal damage and inflammation and had less weight loss than a control group of diseased mice treated with placebo. The compound, MDI-2268, was developed by Daniel Lawrence, PhD, at the University of Michigan. Dr. Stappenbeck remarked of the results, “What’s most exciting here is that SERPINE-1 and its protein seems to be most highly expressed in people with the most severe disease and those who don’t respond to immunosuppressive biologics. No one’s ever thought of targeting something like this. But here we’ve found something that might help lots of people with IBD, especially the ones who aren’t benefiting much from current therapies.”
Read about the discovery and possible implications.
The journal abstract may be read here.
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