New study may improve treatment of IBD patients who do not respond to existing therapies
Led by the University of Oxford researchers, a study reveals a new biomarker of and therapeutic target for inflammatory bowel disease (IBD), a group of disorders in which the intestines become inflamed.
In IBD, the inflammation can lead to symptoms such as abdominal pain, diarrhea, bleeding from the rectum, loss of appetite, weight loss, joint pain, skin problems, and fever. The most common forms of IBD are ulcerative colitis and Crohn’s disease.
It is believed that IBD is driven by perturbed cytokine pathways. Several key mediators involved in IBD pathogenesis have been identified. One such mediator is the cytokine tumor necrosis factor (TNF)-alpha. Monoclonal anti-TNF-alpha antibodies, including infliximab, adalimumab, and certolizumab pegol, have proved to be effective treatments for ulcerative colitis or Crohn’s disease. Currently, anti-TNF-alpha antibodies are mainstay therapies for IBD.
However, about 40% of IBD patients are nonresponsive to anti-TNF therapies. It’s estimated that IBD affects 5 million of people worldwide. So there are approximately 2 million IBD patients that do not respond to anti-TNF therapies. It is imperative to develop new treatments for these patients.
In the new study, the team found that IBD patients express higher levels of OSM and its receptor OSMR in their intestines in comparison to healthy controls, and expression of OSM and OSMR correlates closely with histopathological disease severity. These results suggest that inhibiting OSM might be a treatment strategy for IBD. This hypothesis was confirmed in an animal model of anti-TNF-resistant intestinal inflammation: Inhibition of OSM either through genetic deletion or pharmacological blockade resulted in reduced colitis.
The team investigated more than 200 patients with IBD, some of whom were enrolled in phase 3 clinical trials of anti-TNF therapy. The team found that patients with high OSM expression in gut responded poorly to anti-TNF therapy. Collectively, the data demonstrated that OSM could be a biomarker of and therapeutic target for IBD. This is extremely difficult for IBD patients who are resistant to anti-TNF therapy.
The paper, titled “Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor–neutralizing therapy in patients with inflammatory bowel disease”, is published in the journal Nature Medicine. Cusabio offers OSM and Recombinant TLR2 proteins.