A pill for celiac disease will come soon, researchers believe

Think of a life without freshly baked pastries, pizza straight from a wood-fired oven or beer. For people with celiac disease, these kinds of foods cause them to get bloated and can give them constipation or diarrhoea.

Celiac disease is caused by the body’s reactions to proteins found in wheat, barley and rye.

Lots of activity

Nearly 30 different drug companies are now working intensively to develop a pill or vaccine against the disease.

The Norwegian celiac researchers Ludvig M. Sollid and Knut E. A. Lundin are involved in several of these studies. Thay admit that this may affect their level of optimism.

“With so much activity and so many serious players out there, I think something will emerge that will help people with celiac disease,” Lundin says.

If these efforts are successful, a person with celiac disease could take a pill with enzymes that break down gluten before they eat foods that would ordinarily give them problems, such as pizza.

Another option might be that celiac sufferers would get injections of gluten, with the idea that the immune system will eventually learn to understand that gluten is not a dangerous invader.

One in ten succeeds

The researchers' optimism is partly due to the many large pharmaceutical studies that have come a long way towards developing a drug.

One rule of thumb in medical research is that when pharmaceutical companies work on ten different drugs, only one of them, on average, will come to market.

Sollid and Lundin, who are based at the Rikshospitalet in Oslo, say that some thirty companies have made striking progress. Some are close to the finish line.

One company will present data this autumn. This is a clinical study in which a pill that inhibits the enzyme transglutaminase was tested. Previous research has shown that this enzyme is central to the disease process. Norwegian researchers and nearly 30 Norwegian patients were involved in this study.

But the two researchers know all too well that some of these efforts will fail.

A large vaccine study that showed promising results in the first clinical phase has recently been discontinued following a mid-term review. The results showed no difference in reduction of symptoms or immune activation in those vaccinated with the active substance and those receiving a placebo.

Basic research has pushed boundaries

But Sollid and Lundin's optimism is primarily due to the basic research that has been undertaken during the last decade. Celiac disease is the autoimmune disease that researchers understand best of all autoimmune diseases today.

Much of this research was conducted by Sollid and Lundin themselves.

Lundin, a gastroenterologist, and Sollid, an immunologist, have worked closely to lay the foundation for what we know today about the disease.

When they first began to study the disease in the mid-1980s, they knew relatively little about it.

By the end of the 1980s, Sollid had discovered which genes are involved.

Subsequently, researchers have uncovered the mechanisms of how the disease affects the body. Today, they also know which components of gluten people with celiac disease respond to and which cells in the immune system are involved in the disease.

“We now have very good insight into the disease. Many of our findings have been verified in other laboratories across the globe and are widely cited in international research. It gives us faith that we have pushed the boundaries of what we know and that this knowledge has withstood the test of time,” Sollid says.

He is head of the K.G. Jebsen Centre for Celiac Research at the University of Oslo, where Lundin is a group leader.

Blood test reveals the disease

It is now much easier for the health care system to distinguish people with celiac disease from people who believe they react to gluten, but who don’t actually have the disease.

A blood test can now make the distinction. The test detects antibodies for the enzyme transglutaminase, which is a typical characteristic of untreated celiac disease.

All adult patients who have a positive blood test should also undergo gastroscopy of the duodenum, so that doctors can look for tissue changes.

With these diagnostic tools, many more people have been diagnosed with celiac disease than ever before.

Nevertheless, the researchers don’t think they’ve found everyone with the disease. Many people have stomach aches without understanding what is wrong with them, they believe.

“I think there is a strong underdiagnosis of celiac disease here in Norway,” says Lundin.

Too few get diagnosed

Studies from Sweden and Finland may indicate that celiac disease is far more common than expected.

Later this year, a Norwegian study will release its results on a refined estimate of the incidence in Norway.

The study is analysing 55,000 blood samples from the North Trøndelag Health Survey (HUNT). People whose blood samples test positive will be invited to get a gastroscopy to confirm the diagnosis.

The researchers do not want to speculate on the results, but they say the preliminary results look exciting.

More insight into other diseases

Understanding celiac disease is not only important for people with the disease. It’s also becoming important in understanding other immune disorders.

Last year, researchers found that the same immune cells that respond to gluten in celiac disease are found in patients with other autoimmune diseases.

This is true for arthritis, MS, type 1 diabetes, systemic sclerosis and psoriasis.

“The underlying immune mechanisms of these diseases are probably very similar,” Sollid says.

The only disease that is understood

But celiac disease is the only one of these autoimmune diseases where scientists know exactly why the immune system’s soldiers are converted into weapons: The body thinks gluten is dangerous.

The immune cells that guard against intruders are called T cells.

When T cells attack, they cause inflammation of the small intestine. This causes the intestinal villus to disappear and the bowel to become inflamed. This reaction impairs the intestine’s ability to absorb nutrients from food.

Over the long term, this can cause the patient to suffer from fatigue and iron and calcium deficiencies, which can have long-term health consequences. People with untreated celiac disease are likely to have a slightly increased risk of dying earlier.

Not born with celiac disease

Although scientists now know much more about celiac disease than other autoimmune diseases, there is still a great deal they don’t understand.

They know that the disease is partly hereditary. Everyone with celiac disease has special tissue types, called HLA-DQ2 or HLA-DQ8.

But even if you are born with a hereditary predisposition to celiac disease, it is far from certain that you will develop it.

People with celiac disease are born with a very normal immune system. But at some point, their immune system suddenly attacks gluten. In most people, this happens during childhood, but for many, the diagnosis is made only in adulthood, the researchers say.

Their research has shown that once the immune response has started, the disease is established, and you have it for life.

But why some people develop the disease and others do not remains a mystery.

“Studies in twins have shown that the incidence of celiac disease in identical twins is very high. Genes undoubtedly play an important role. But there must be something more. You are not born with the immune reaction, it happens when you are exposed to something in the environment,” says Sollid.

Many things have small effects

What’s less understood is what environmental factors cause the body to develop the disease.

“There are a whole range of environmental factors that on their own mean very little,” Lundin says.

Some of these factors include how many antibiotic courses you have had, or if you have had a stomach virus, or if your mother took iron when she was pregnant.

"Many things have a very small effect, but it is the total environmental impact that we believe makes you develop celiac disease," he says.

What researchers know is that the incidence of celiac disease, like other autoimmune diseases, is very different from country to country.

Finnish researchers have found that there are far more Finns in Finland who have celiac disease than in Russians who live east of Karelia, even though these people share a common genetic origin. There is also much less celiac disease in the Baltic countries. But as these countries adopt a more Western lifestyle, the incidence of the disease is approaching that in the Nordic countries.

Careful with recommendations

This strengthens the researchers' hottest explanation for the cause, the so-called hygiene hypothesis.

This hypothesis suggests that we come in contact with many fewer bacteria and fewer types of bacteria in our very hygienic society than we did just a few decades ago. Our immune system doesn’t get as much of a workout as it used to. It may therefore think that innocent substances such as birch pollen and gluten are dangerous invaders.

While the researchers don't quite know what triggers celiac disease, they also don't know what advice to give patients who have a hereditary predisposition, so that they can avoid getting sick.

Researchers have studied children who are at high risk of celiac disease because their parents and siblings have it. In these studies, they have found no connection between the early or late introduction of gluten on the risk of the child developing celiac disease. Nor does breastfeeding seem to matter.

“There are no certain ways to influence the development of celiac disease. We thus have to be careful about the recommendations we make,” says Lundin.

One group that’s not understood

Another challenge is that while researchers are getting a much better understanding of celiac disease, more and more people are reporting that they react to gluten.

“In many ways, this has made it more difficult to study people who react to gluten,” says Sollid.

“We know a lot about celiac disease and have good diagnostic methods. But we have less to offer to people who react to gluten but don’t have celiac disease,” Sollid says.

“We as doctors always want to believe our patients when they say something is bothering them. That’s our starting point,” he said.

But the challenge with this situation is that there is no diagnostic test. Some people say they react to gluten, even though there is no evidence of this in their blood test, and they have no bowel damage.

Some have IBS

Some of these individuals likely have irritable bowel syndrome. Between 10 and 15 per cent of the population has mild to very severe problems that don’t show up in blood tests or in the gut.

In a study the researchers published last year that was cited by the Norwegian Celiac Disease Association, a blind test was conducted with 59 people who were gluten-free and had bowel problems. The researchers gave them muesli bars, some of which also had added gluten while others contained fructan — a sugar compound that is also found in the grain.

They found that almost none of the participants reacted to gluten, while many reacted to fructan.

In other words, it may not be gluten that is the problem for these patients.

Translated by: Nancy Bazilchuk

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Read the Norwegian version of this article at forskning.no