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Modified bacteria target inflammatory bowel disease

14 Feb, 2013

ViThera Pharmaceuticals, a startup biotechnology company based in Cambridge, Massachusetts, recently announced the publication of results demonstrating a novel treatment of inflammatory bowel disease (IBD).

Inflammatory bowel disease

IBD is a group of disorders in which the intestines become inflamed, causing severe or chronic gut pains and often bloody diarrhoea, weight loss, loss of appetite, bleeding from the rectum, fever and fatigue. The most common forms of IBD are ulcerative colitis and Crohn’s disease. According to Crohn’s and Colitis New Zealand, New Zealand has one of the highest incidence rates of IBD in the world, with approximately 15 000 sufferers. IBD affects people of all ages but onset typically occurs between the ages of 15 and 35 years.

Modified lactic acid bacteria

The US researchers have successfully genetically engineered two food-grade strains of lactic acid bacteria (LAB) to express and deliver a protein called Elafin. Elafin is a natural protease inhibitor expressed in healthy intestinal mucosa and has anti-inflammatory properties in vitro and in animal models. In their report the researchers noted that mucosal expression of Elafin is diminished in patients with IBD. “This defect is associated with increased elastolytic activity (elastase-like proteolysis) in colon tissue.”

Bacteria reduced inflammation

In separate trials using mice (where the modified bacteria were orally administered) and human cell cultures from IBD patients, the bacteria reduced signs of inflammation and “restored intestinal homeostasis” in mice. The trials also found that, “when cultures of human intestinal epithelial cells were treated with LAB secreting Elafin, the inflamed epithelium was protected from increased intestinal permeability and from the release of cytokines and chemokines, both of which are characteristic of intestinal dysfunction associated with IBD.”

The protein occurs naturally in the gut of healthy people. According to the researchers, the protein manufactured by the bacteria is safe and with further testing and development could potentially be taken in the form of a pill or in foods like yoghurt to treat IBD.

Research published

In a press release from the company, ViThera announced they had obtained worldwide exclusive rights to the technology and are developing it further towards validation in clinical trials.

The research was published in the journal Science Translational Medicine on 31 October 2012.

Coincidentally, Nature magazine published a paper on 1 November 2012 on genetic variants associated with IBD, which has identified 71 new sections of the genome linked to the disease. The international study, which included data from New Zealand, reveals that there are many similarities in the underlying biological process for different forms of IBD. However, while genes may explain some susceptibility to disease, the authors note that environmental factors – such as gut microbes – may play a large role.

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