Oncostatin-M: A novel therapeutic target for inflammatory bowel disease

The symptoms of inflammatory bowel disease (IBD) are currently poorly managed by anti-TNFα therapy, with only 60% of patients responding to this ‘gold-standard’ treatment. Other treatments, such as anti-inflammatory drugs, have associated adverse effects making them undesirable to use. Therefore, there is a need for new therapeutics to treat IBD.

Researchers at Oxford have found that Oncostatin-M (OSM) has a major role in an inflammatory pathway thought to underlie IBD, and so novel drugs to treat IBD may be designed around targeting OSM and its receptor. OSM levels were also found to be indicative of disease allowing a novel method of diagnosis as well as prognosis. Furthermore, a patient’s response to anti-TNFα therapy correlated with their levels of OSM and so could serve as a method of determining first-line treatment options.

Inflammatory bowel disease (IBD) is a term that encompasses a group of diseases, including Crohn’s disease and ulcerative colitis, which affect the colon and small intestine. These are debilitating chronic disorders affecting more than 300,000 people in the UK. Patients with IBD suffer periodically with mild to severe symptoms with intermittent remission. There is currently no cure, and so treatments traditionally focus on managing the symptoms by hindering the immune response that drives the disease. Traditionally treatments include anti-inflammatory drugs, but these lack specificity and cause gastrointestinal toxicity.

The current ‘gold-standard’ therapy

Modern treatments, such as monoclonal antibodies against Tumour Necrosis Factor-α (TNFα), induce and sustain remission by targeting components of inflammatory pathways that are thought to be more specific to IBD. However 40% of patients subjected to this therapeutic regimen do not respond, and up to a further 60% of those that initially respond fail to respond to repeat treatments. These patients are left unable to control their IBD and will eventually require surgery. Anti-TNFα therapy is the current gold-standard treatment for patients with IBD but alongside their low response rate, they also cause immunosuppression. Therefore, there is an obvious need for new therapeutics to treat IBD.

Targeting a solution

Researchers at Oxford University have identified a potential new target for IBD therapeutics; they found Oncostatin-M (OSM) to be a major component of the cytokine response in the Th17 inflammatory pathway. This pathway is thought to be critical in the pathogenesis of IBD, therefore targeting OSM or its receptor may offer a more effective treatment for a greater proportion of IBD patients.

Additionally, the researchers found that levels of OSM may indicate whether a patient has IBD and whether a patient in remission will have a recurrence of symptoms. Furthermore, the level of OSM correlated with patient response to anti-TNFα therapy and so could be used to determine the most appropriate first-line treatment for IBD and other TNFα-mediated conditions.
Altogether, this research has discovered novel methods to diagnose, prognose and treat IBD which could revolutionise the care of patients suffering from the disease.

Commercialisation

Oxford University Innovation has filed a patent (PCT/GB2016/050185) on this technology. The associated publication can be accessed here: https://www.nature.com/articles/nm.4307

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