New research suggests that a small protein involved in inflammation could be an effective target for drugs to treat inflammatory bowel disease, with particular benefit for the millions of patients who do not respond to the current standard therapy.
The study – led by the University of Oxford in the United Kingdom – is published in the journal Nature Medicine.
Inflammatory bowel disease (IBD) is a general term for long-term conditions that cause painful inflammation in the digestive tract or gut.
The two most common forms of IBD are ulcerative colitis, which affects the large intestine, and Crohn’s disease, which affects the whole of the digestive tract.
In IBD, the immune system mistakenly attacks the cells of the intestines, giving rise to chronic inflammation. However, exactly why this happens is not well understood.
IBD is usually diagnosed early in life. Symptoms include pain and diarrhea, as well as blood passing from the rectum. Because it affects the gut’s ability to absorb nutrients, the disease can also contribute to anemia.
Estimates suggest that there are more than 1 million people in the United States and 2.5 million in Europe living with IBD.
The disease has also emerged in newly industrialized parts of the world, and it has evolved into a global disease that is increasing in every continent.
Although treatment of IBD incurs a substantial healthcare cost, this does not reflect the toll it takes in terms of diminished quality of life, social stigma, and the career aspirations that are often cut short for those living with the disease.
- Due to lack of standard diagnostic criteria, it is difficult to estimate how many people have IBD.
- Crohn’s disease is more common in people who smoke.
- Ulcerative colitis is more common in ex-smokers and never-smokers.
While anti-TNF therapy has been the standard of care for IBD for nearly 20 years, up to 40 percent of those affected do not respond to it, and there is an urgent need to find new therapies for the millions of people affected.
The new study concerns the cytokine Oncostatin M (OSM) – a small immune system protein that helps to regulate inflammation. It is also involved in liver and heart tissue repair.
However, excessive production of OSM has been linked to a number of diseases, including atherosclerosis, skin and lung inflammation, and several types of cancer. It is also thought to be involved in arthritis.
The researchers note that previous studies have already proposed cytokines as treatment targets for cases in which anti-TNF therapy is ineffective, but they have not found any that work well for IBD.
This is the first study to show that patients with IBD have more OSM in their guts than healthy controls, and also that those with the highest levels were most likely to be unresponsive to anti-TNF therapy.
The researchers found that by measuring levels of OSM in samples of gut tissue, they could predict which patients taking part in an anti-TNF therapy trial would not respond to treatment.
They also found that deleting genes for OSM or blocking the cytokine with drugs significantly reduced colitis in mice.
Lead researcher Prof. Fiona Powrie, director of the Kennedy Institute of Rheumatology at Oxford, says that it is very important to find new therapies for the 2 million or so IBD patients worldwide who do not respond to the current treatment.
“The identification of OSM as a new disease mediator in these patients offers hope for new therapies that can be tested in the clinic,” Prof. Powrie notes, as she concludes:
“This is a very important finding, because at the moment we are unable to predict which patients will respond well to current therapies; this has an impact on the care we are able to provide to these patients.”
The team believes that not only could OSM serve as a target for new drugs to treat IBD, but it could also serve as a marker to predict which patients will respond to which therapies.