Toxic Trio Identified as the Basis of Celiac Disease

Walter and Eliza Hall Institute scientists have identified the three protein fragments that make gluten – the main protein in wheat, rye and barley – toxic to people with coeliac (spelled Celiac in North America) disease.

Their discovery opens the way for a new generation of diagnostics, treatments, prevention strategies and food tests for the millions of people worldwide with coeliac disease.

When people with coeliac disease eat products containing gluten their body’s immune response is switched on and the lining of the small intestine is damaged, hampering their ability to absorb nutrients. The disease is currently treated by permanently removing gluten from the patient’s diet.

Dr Bob Anderson, head of the Walter and Eliza Hall Institute’s coeliac disease research laboratory, said it had been 60 years since gluten was discovered to be the environmental cause of coeliac disease.

“In the years since, the holy grail in coeliac disease research has been to identify the toxic peptide components of gluten; and that’s what we’ve done,” Dr Anderson said.

The research, done in collaboration with Dr Jason Tye-Din, Dr James Dromey, Dr Stuart Mannering, Dr Jessica Stewart and Dr Tim Beissbarth from the institute as well as Professor Jamie Rossjohn at Monash University and Professor Jim McCluskey at the University of Melbourne, is published in today’s issue of the international journal Science Translational Medicine.

The study was started by Professor Anderson nine years ago and has involved researchers in Australia and the UK as well as more than 200 coeliac disease patients.

The patients, recruited through the Coeliac Society of Victoria and the Coeliac Clinic at John Radcliffe Hospital, UK, ate bread, rye muffins or boiled barley. Six days later, blood samples were taken to measure the strength of the patients’ immune responses to 2700 different gluten fragments. The responses identified 90 fragments as causing some level of immune reaction, but three gluten fragments (peptides) were revealed as being particularly toxic.

“These three components account for the majority of the immune response to gluten that is observed in people with coeliac disease,” Dr Anderson said.

This knowledge has already been used by Melbourne-based biotech company, Nexpep Pty Ltd, to develop a ‘peptide-based’ immunotherapy that aims to desensitise people with coeliac disease to the toxic effects of gluten. Nexpep’s Phase 1 trials of the therapy were completed in June and final results are expected in coming months.

The immunotherapy works by exposing people with coeliac disease to small amounts of the three toxic peptides and is based upon the same principles as desensitisation for allergies.

Dr Anderson said although coeliac disease could be managed with a gluten-free diet, compliance with the diet is often challenging and nearly half the people on the diet still have residual damage to their small intestine. “Consequently, the immunotherapy and three other drugs are under development to help people with coeliac disease.”

Full Press Release
Photo Credit: Czesia Markiewicz, Walter and Eliza Hall Institute

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  • Josh says:

    My wife has Coeliac disease and I am truly happy for this breakthrough! I can't wait until we see the medicine and how it will all affect her intestines!

    THANK YOU GUYS!!!!!!!!

  • dhkinil says:

    My mother, who passed away more than 12 years ago, suffered terribly from this disease. I know first hand how terrible it is and can only hope this is truly the answer.

  • Mrs Mary Ellen Johns says:

    I am not yet diagnosed with Coeliacs but have all the symptoms plus I get the same symptoms when I eat potatoes! I am waiting for the results of biopsies and wonder if there are any of these peptides in potatoes as well? I do hope this is the start of relief for others who suffer and would like to thank those who work so hard to find a cure for this awful condition.

  • Rhonda says:

    Mary, you may have Celiac but the potato issue makes me think you may also have a bacterial imbalance in your intestines. I have Celiac but because my digestive tract was so messed up, once I started eating gluten free I also had to do some reparative work by eating foods that promote good bacteria and yeast balance and eliminate the bad (the ones that make you gassy). Potatoes may have to go for awhile. You may also want to get rid of dairy for a bit and start taking a tablespoon of straight acidophilus for a couple months. Best of luck to ya!

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