Researchers from the French National Institute for Agricultural Research (INRA) and the French National Institute of Health and Medical Research (INSERM) have developed a strategy to deliver the human protein elafin – a protease inhibitor – into the guts of mice to reduce inflammatory symptoms associated with celiac disease.

Using a food-grain strain of L. lactis​ for delivery, the researchers proved that the molecule prevented the destruction of the gut barrier during inflammation and interacted with enzymes responsible for the abnormal breakdown of gluten: transglutaminase-2. Findings were published earlier this week in the American Journal of Gastroenterology.​

The teams described the findings as promising in the battle against celiac disease​ which was currently incurable and managed only by a strict gluten-free diet.

However, speaking exclusively to BakeryandSnacks.com, INRA’s research director Philippe Langella said that continuing research in humans would be more complex because the bacterium to deliver the elafin had been genetically modified.

EU law bans the use of genetically modified foods, except for use of certain approved GM crops​ which even then must be labeled.

“Now, what we have to do is convince the European Food Safety Authority (EFSA) to allow us to do a technical human trial and for this, it’s a bit difficult as we are using GMOs,”​ he said.

EFSA assesses GMO submissions on a case-by-case basis and then reports scientific findings to the European Commission who can then draft proposals to grant or refuse authorization.

Finding a natural bacterium that has the same in-gut impact will be extremely difficult to do, says Langella

GMO bacterium is the most efficient delivery system​

However, Langella said that a genetically modified bacterium was the best method to deliver elafin into the human gut.

“It’s probably the most convenient, it’s very easy to produce using local production and the delivery, importantly, will be at the site of inflammation. Compared to, for example, an oral administration of elafin which would be difficult to produce and difficult to protect from the stress in the gastric tract.”​

“The ideal would be our recombinant bacteria because natural bacteria won’t necessarily release the right protease inhibitors,”​ he said. Although, he added that the teams would use a more powerful and persistent bacterium strain – Lactobacillus​ – for the human gut.

Despite this, Langella said the teams could investigate natural bacterium delivery if authorization to use the GMO bacteria was too difficult, but added it would be “long and fastidious research”.​

“There are already some strains which are able to naturally produce proteases inhibitors, so these strains should now be tested and we’re trying to test them in order to see if we can get as close a match to the effects seen with our recombinant bacteria. But it will be very difficult to find a bacteria protease inhibitor that will be efficient on the gut proteases in the same way,”​ he said.

The GMO hurdle: Authorities and the consumer…​

Langella said use of genetically-modified organisms should always be carefully considered.

“We should be very careful. Right now, we can limit the dissemination of GMOs in an external environment but we have no data on the long-term use of GMOs in humans. That’s why we’ve targeted our strategy towards incurable diseases…I think the difficulties of using GMOs in humans and animals should be restricted and limited to incurable diseases.”​

Celiac disease has no cure and a life-long gluten-free diet can be costly and difficult, says Langella

For an incurable disease like celiac disease, any solution – GMO or other – should be seriously considered, he said.

“For celiac disease, we have no cure. The gluten-free diet is a very heavy and costly solution and it’s hard to live with. So we think that the use of our GMO bacteria could probably be best in the long-term for these patients.”​

There had already been significant interest from irritable bowel disease (IBD) sufferers, following earlier research published in 2012 proving the efficacy of elafin against IBD symptoms in mice, he said, with many people ready and willing to take part in human trials.

In time, he said the same reaction would be expected following the celiac disease findings.

Industrial and financial partners needed to push into human research​

Langella said INRA was looking for industry partners to team up with to work towards human clinical trials to test elafin in the treatment of celiac disease. “We’re also searching for investor partners too, because it will be very expensive,”​ he said.

He said INRA was open to working with companies from anywhere in Europe.

INRA already secured US Boston-based ViThera as its partner for exclusive license rights on its earlier elafin for IBD patent. The firm was currently trying to raise funds to do clinical trials in IBD patients, Langella said.