Two new studies are offering novel insights into celiac disease, the autoimmune disorder triggered by exposure to gluten. One study from University of Sheffield researchers is suggesting immune responses to gluten in celiac sufferers can lead to neurological damage, while another new study offers hope for a cure, describing the mechanisms by which a nanoparticle treatment can induce immune tolerance.
Celiac disease is thought to primarily manifest as a gastrointestinal condition, although it can be associated with other autoimmune disorders such as diabetes. Over the last couple of decades some researchers have begun to suspect celiac disease can be associated with neurological abnormalities. These can include observable cognitive deficits and psychological issues such as depression, or clear physiological abnormalities detectable in brain imaging data.
A new study, led by a team from the University of Sheffield, is offering the strongest evidence to date of a causal link between celiac disease and neurological damage.
Prior research on the topic has been criticized by some as suffering from what is called ascertainment bias, a kind of sampling bias where certain members of a target population are more, or less, likely to be included in a study depending on the initial hypothesis. In order to eliminate the potential of ascertainment bias the researchers dug into an independent dataset from the UK Biobank, a massive long-term health study following half a million subjects.
The new research utilized UK Biobank data from over 100 celiac disease subjects, compared to an age-matched control group of around 200 subjects. Data from a number of mental health and cognitive tests were evaluated as well as analyses of MRI brain scans.
“For the first time, the study offers some clarity on the fact that there does appear to be the risk of neurological damage for people living with CD [celiac disease], driven by their autoimmune response to gluten exposure,” says Iain Croall, one of the researchers working on the project. “Our independent UK Biobank participants with CD showed meaningful neurological and psychological deficits when compared with control participants. The data from the CD group of participants showed a significant reaction time deficit, compared to the control participants; alongside signs of anxiety, health-related unhappiness and depression.”
Croall suggests the detection of this correlation in an independent dataset such as the UK Biobank is a validation of previous research linking celiac disease with neurological changes. The hypothesis presented in the research is that the inflammatory responses triggered by gluten exposure can subsequently cause neurological damage.
And, the study suggests this neurological damage is cumulative with some population studies noting celiac disease subjects are at a higher risk of developing vascular dementia in their senior years. Croall says these findings are not cause for concern, but instead affirm the importance of celiac disease subjects avoiding gluten exposure where possible.
“What the research shows is that it would be of great benefit for clinicians to support people living with CD to be as vigilant as possible with their gluten-free diet,” says Croall. “Reducing any accidental exposure to gluten controls any further brain damage and promotes healing within the digestive system safeguarding a better level of overall health.”
Another newly published study is offering hope of a possible celiac disease cure, describing the pre-clinical results of animal research testing a nanoparticle treatment designed to induce immune tolerance to gluten. The research was led by scientists from the University of Helsinki and focused on developing a way to gently introduce gliadin into the systems of celiac subjects without triggering a major immune response.
The treatment involves encapsulating gliadin molecules inside a biodegradable nanoparticle. The human body responds innocuously to the presence of the nanoparticle, treating it like harmless debris, and sending an immune cell called a macrophage to clean it up.
When the body breaks down the nanoparticle and is confronted with the gliadin antigen, the research has shown no immune response is triggered. The process has been described as essentially reprogramming the immune system to be tolerant of certain molecules that would previously trigger inflammatory responses.
The new study, published in the journal Gastroenterology, describes the expansive pre-clinical testing of the treatment, demonstrating the efficacy of the nanoparticles in three different celiac disease animal models. The treatment was shown to be successful, reducing inflammatory markers and inducing immune tolerance to gliadin.
Perhaps the most important point here is that although these results have only just now been published in an academic journal, the data proved so promising in its early stages it was granted Fast Track designation by the FDA, and has already commenced human clinical trials.
Early human trial safety data was revealed late last year, demonstrating exciting potential. So much potential in fact, that a major pharmaceutical company jumped into the game and paid US$420 million to acquire global licensing to the treatment.
So, this is not simply another abstract nanoparticle innovation demonstrating a prospective cure based on a few animal tests. This is a real potential cure, deep into Phase 2 human trials right now. Early data from these trials suggest the nanoparticle treatment is safe, and significant reductions in inflammatory markers point to potential efficacy. Clinical applications may be still years away, and reliant on larger more expansive trials, but it’s a hopeful step in the right direction.
The neurological damage study was published in the journal Gastroenterology, as was the nanoparticle treatment study.