Avoiding exposure to gluten is essential for people with coeliac disease. The condition is a lifelong autoimmune disease that causes the immune system to react to gluten.
It produces a range of unpleasant symptoms including bloating, diarrhoea, constipation, nausea, tiredness, sudden weight loss and mouth ulcers.
If left untreated, coeliac disease can lead to complications such as neurological conditions, osteoporosis anaemia and, rarely, small bowel cancer and intestinal lymphoma.
Inadvertent exposure to gluten
Even very small amounts of gluten can be damaging to someone with coeliac disease but totally avoiding gluten exposure is virtually impossible to achieve.
Contamination with gluten can occur during cooking and food preparation, food processing, food packaging and as a result of poor labelling. Gluten can even be found in medicines, toothpaste and lipstick.
Inadvertent exposure to gluten in everyday life, leads to half of coeliac patients continuing to experience mucosal inflammation despite following a gluten-free diet.
Research shows promising results
But now trials on an experimental new drug offers the hope of reducing symptoms from people with coeliac disease who are exposed to gluten.
A phase 2 proof-of-concept study provided promising evidence that AMG 714 (Amgen/Celimmune) – an investigational monoclonal antibody – can block interleukin (IL-15).
This is exciting news because IL-15 is a key driver of the key immune cells in our gut (the intraepithelial lymphocytes) that causes it to react to gluten in people with coeliac disease. It can also cause the intraepithelial lymphocytes to become malignant which can lead to lymphoma.
AMG 714 works by preventing signals on the cell surface, interrupting the activation and proliferation process of the intraepithelial lymphocytes.
In a double-blind trial Francisco Leon MD PhD, who led the research, found that doses of AMG 714 (both 150mg and 300mg) reduced the effects of gluten in patients with coeliac disease compared to a placebo.
Intestinal inflammation was less and there was a trend towards reduced intestinal damage, although not sufficient to be statistically significant.
Patients in the trial were randomly assigned to receive one of two doses of the AMG 741 – either 150mg or 300mg or a placebo, administered subcutaneously six times over 12 weeks. One subgroup of 49 patients was given around 2.5g of gluten daily for 12 weeks. Another subgroup with baseline mucosal atrophy tested positive for gluten contamination and was not given additional gluten.
No participatns who received gluten during the test and received a 300 mg dose of AMG 714 had active disease at week 12 whereas one third of the placebo group did.
Those who took AMG 714 also had significantly better Coeliac Disease Patient Reported Outcome scores compared with the group who took the placebo.
The potential to protect against accidental exposure
Further research is now underway to determine the optimum dosage of AMG 714.
The researchers are keen to stress that the drug is being tested for its potential to protect against accidental exposure to modest levels of gluten, and not the deliberate consumption of large amounts.
The hope is that coeliac patients who are following a gluten-free diet will experience fewer gluten-triggered episodes as a result of taking the drug.