Helsinki: In a development that might bring much relief to celiac disease patients in the long run, University of Helsinki researchers have developed a nano-particle, gliadin, that will allow patients to consume gluten diet, which is otherwise not recommended for such patients.
Celiac disease or celiac disease is a long-term autoimmune disorder that primarily affects the small intestine. Celiac disease affects 0.3-2.4% of people in most countries worldwide. Celiac disease is caused by a reaction to gluten, a group of various proteins found in wheat and in other grains such as barley and rye. The only available treatment for celiac disease till date is a life-long gluten-free diet.
Recently, Immunologist Tobias Freitag co-developed and tested nanoparticles containing gliadin for the immunomodulatory treatment of celiac disease in Professor Seppo Meri's research group at the University of Helsinki, in collaboration with industry.
When injected into the blood of mice in three different celiac disease models, absorbable, spherical, 500nm gliadin nanoparticles (TIMP-GLIA) significantly reduced markers of gliadin-specific T cell activation, inflammation, and tissue damage. Gliadin nanoparticle treatment also induced gene expression profiles associated with immune tolerance. These findings support the concept that it may be possible to "reprogram" the immune system in celiac patients and to instruct T lymphocytes to tolerate gluten again. If this would result in clinical unresponsiveness to gluten-containing diet in trials with celiac patients, TIMP-GLIA treatment could lead to the cure of celiac disease. Patients may then be able to eat normal food again without harmful consequences.
The gliadin nanoparticle project at the University of Helsinki was conducted in collaboration with Cour Pharmaceutical Development Company, Inc. A license for the development of TIMP-GLIA has since been acquired by Takeda Pharmaceuticals. Project results informed early clinical trials in celiac patients conducted in the US. Results from these clinical trials were demonstrated at UEG Week 2019 in Barcelona. Based on these results, the treatment of celiac disease patients with TIMP-GLIA silences or reduces inflammatory gliadin-specific T cells in the blood.
The pre-clinical results in mice have now been published as an article in press in the scientific journal Gastroenterology.
Similar nanoparticles may also be developed for the treatment of other autoimmune diseases, e.g. diabetes, multiple sclerosis or narcolepsy. However, this is under a precondition that the underlying disease-causing factor is known.
"The exact reasons that may explain why some people develop celiac disease are unknown, but only about 30-40% of the population is at risk to develop celiac disease, based on identified genetic predispositions" said Freitag .
Classic symptoms include gastrointestinal problems such as chronic diarrhea, malabsorption, loss of appetite and among children failure to grow normally abdominal distention
Diagnosis is typically made by a combination of blood antibody tests and intestinal biopsies, helped by specific genetic testing.
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Tobias L. Freitag et al. Gliadin Nanoparticles Induce Immune Tolerance to Gliadin in Mouse Models of Celiac Disease. Gastroenterology, 2020 DOI: 10.1053/j.gastro.2020.01.045