The Outlook in Coeliac Disease

The outlook and future treatments for coeliac disease

Most in the professional coeliac community believe that alternatives to the gluten-free diet (GFD) are urgently needed, largely because the diet is expensive and difficult and because compliance with it sometimes poor. Further, coeliac disease (CD) is on the rise worldwide and there is concern that this will increasingly burden health-care providers, adding to the demands placed upon them by low diagnosis rates.

Future treatments for coeliac disease 

There are four possibilities:

  1. Coeliac disease treatments that work in addition to a gluten free diet
  2. Coeliac disease treatments that minimize possible health effects of hidden, trace or accidentally consumed gluten in the gluten free diets
  3. Treatments for coeliac disease that allow moderate gluten consumption 
  4. Treatments for coeliac disease that replace the gluten free diet and allow a regular diet.

There are various treatments being proposed, developed and trialled at the beginning of the second decade of the new millennium, and some are considered below. It has been speculated that it may not be until 2020 that one or more become widely available commercially. Some may fail at trial stage if, for instance, unacceptable side-effects should be encountered, but even a single viable one could transform lives – if only by offering greater peace of mind and reduced risks of the usual effects of cross-contamination when dining out.

Vaccine therapy

Of the many thousands of protein parts (peptides) found in gluten, the bulk of the immune response activated in coeliac disease is caused by just three, and it is these three that are most toxic to coeliacs. From this starting point, scientists at the Walter and Eliza Hall Institute in Melbourne, Australia, led by Dr Robert Anderson, have developed a potential vaccine, Nexvax2, which has been synthesized to work by ‘introducing’ these fragments of gluten to the immune system of coeliacs in a particular way, ‘re-educating’ them to tolerate the protein and not to react inappropriately. It has the potential to treat 80 per cent of those with CD, say the researchers.

Enzyme therapy

Alvine Pharmaceuticals’ enzyme treatment, ALV003, is a therapy that helps to break down the toxic fragments of gluten in the stomach when taken before a gluten-containing meal. Other protein enzymes – called proteases – may also have potential in the development of new ‘free-from’ foods, serving to ‘pre-digest’ gluten in order to formulate more palatable products.

Helminthic therapy

Not for the squeamish, this involves inoculating coeliac disease patients with a harmless hookworm to interfere with immune responses and alter responsivity to gluten. This is based on the idea that our sterile Western modes of living and antibiotic-rich medicine cabinets, which have eradicated intestinal parasitic worms from our bodies, have detrimentally affected our immune responses, increasing the tendency towards autoimmune conditions such as coeliac disease. Kept ‘distracted’ by these parasites, the immune system ought to ignore the mistaken ‘threat’ of gluten, holds the theory.

Other therapies

AT-1001 (larazotide) is a promising drug that blocks the action of zonulin, a protein that ‘unlocks’ the intestinal barrier and increases the gut’s permeability, or leakiness. Those with autoimmune disease produce higher levels of zonulin. Alba Therapeutics Corporation in the US, founded by Dr Alessio Fasano of the University of Maryland Center for Celiac Research, has conducted promising trials.

Meanwhile, CCX282-B is an anti-inflammatory drug that works by restricting the movement of certain immune cells – which trigger the coeliac response – from the bloodstream into the gut wall.

Prevention

The maxim certainly applies: prevention is clearly better than cure.

Probiotics

It has been theorized that the balance of bacteria that we all carry naturally in our digestive system could have relevance in the development of coeliac disease, given that many people show the first symptoms of the disease when this balance has been upset – following gastrointestinal surgery, for instance, or food poisoning. Correcting this upset with the introduction of certain probiotics could lead to a potential preventative treatment.

Optimized gluten introduction

When is the best time to introduce gluten into an at-risk baby’s diet in order to induce tolerance? A few studies have looked at this vital unanswered question, and results appear to indicate that there may be a ‘window of opportunity’ at between four and six months that may be ideal. Further prospective studies are ongoing. The quantity of gluten given at various stages may also be a factor.

An Italian trial, though, found that delayed introduction to one year was associated with a considerably lower risk of developing coeliac disease after five years than introduction at six months – although further follow-up for many years will be needed as this may not indicate a different lifetime prevalence.

Other vaccination

Children genetically predisposed to coeliac disease appear more likely to develop the disease after a rotavirus infection – opening the possibility that an anti-rotavirus vaccine may offer some protection in a subset of infants.

New wheats and breads

Genetic modification of wheat is potentially revolutionary. Some researchers have suggested it may be possible to ‘breed out’ the toxic elements of gluten, rendering a wheat safe for consumption by all.

Older and more ‘natural’ forms of wheat may also be exploited, as these are known to be less toxic than modern types of wheat, which have been bred for their rich gluten content and associated culinary properties.

The use of Lactobacillus bacteria in sourdough bread has also aroused interest: it appears in pilot studies that these bacteria can break down toxic gluten peptides, rendering the bread safe, or at least safer, but further studies are needed.

Diagnosis

The debate over whether a biopsy should be required to diagnose coeliac disease remains active. Some feel that a combination of increasingly reliable blood tests and strong clinical symptoms should be sufficient in at least a proportion of cases; others feel that a biopsy should remain mandatory.

New and improved tests could eventually make the question redundant. A test for antibodies to the three peptides found to be most toxic is one possible avenue. Another test to detect certain proteins in the urine – also a future possibility – would be even less invasive.

CD-Medics is a European project developing a point-of-care test to measure both coeliac antibodies and genes.

Diagnostic criteria are likely to remain in flux for some time, and revisions to recommendations will be inevitable.

Screening

Screening is a strategy used to look for disease where no signs of it exist. Screening for coeliac disease in at-risk groups (e.g. first-degree relatives of patients) is recommended, and this ‘case-finding’ can be highly effective. But should universal screening – that is, screening of the whole population for coeliac disease – be implemented? It is a future possibility, with some arguing that a coeliac test should become as routine as a cholesterol test.

Controversies

Inevitably in such an active field, there is much disagreement and debate.

Some experts feel that research would be better geared towards the development of more innovative gluten-free (GF) foods – not drugs and vaccines. Some coeliacs, equally, are quite happy to live a gluten free lifestyle, aren’t interested in a future of wheat reintroduction, but would welcome wider and more affordable choices from the supermarket.

The issue of screening is widely debated. Obviously, this would help to diagnose coeliacs and find the missing millions we know are out there, but on the other hand, there is the moral concern that it would ‘impose’ disease on people who may consider themselves healthy and not wish to know otherwise. The burden on health care must also be considered.

Genetic modification of wheat is obviously controversial.

Moving forward

Never before has coeliac disease been the subject of so much attention, or been so visible in the public domain. It is impossible to predict what its future may be, or what implications this will have for those with the disease or at risk of developing it. What is indisputable is that the increasingly conspicuous profile of coeliac disease can only be regarded as a very good development indeed.