Results of a new phase 2 clinical trial using technology show it is possible to induce immune tolerance to gluten in individuals with coeliac disease. The findings may pave the way for treated coeliac patients to eventually tolerate gluten in their diet.
In the study presented at the European Gastroenterology Week conference in Barcelona, Spain, patients were able to eat gluten with a substantial reduction in inflammation after treatment with the technology and the results also show a trend toward protecting patients' small intestine from gluten exposure.
The technology is a biodegradable nanoparticle containing gluten that teaches the immune system the antigen (allergen) is safe. The nanoparticle acts like a Trojan horse, hiding the allergen in a friendly shell, to convince the immune system not to attack it.
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Beyond coeliac disease, the finding sets the stage for the technology - a nanoparticle containing the antigen triggering the allergy or autoimmune disease - to treat a host of other diseases and allergies including multiple sclerosis, type 1 diabetes, peanut allergy, asthma and more.
The technology was developed in the lab of Stephen Miller, professor of microbiology and immunology at Northwestern University Feinberg School of Medicine, who has spent decades refining the technology.
"This is the first demonstration the technology works in patients," said Professor Miller, the Judy Gugenheim Research Professor of Microbiology and Immunology. "We have also shown that we can encapsulate myelin into the nanoparticle to induce tolerance to that substance in multiple sclerosis models, or put a protein from pancreatic beta cells to induce tolerance to insulin in type 1 diabetes models."
When the allergen-loaded nanoparticle is injected into the bloodstream, the immune system isn't concerned with it, because it sees the particle as innocuous debris. Then the nanoparticle and its hidden cargo are consumed by a macrophage, essentially a vacuum-cleaner cell that clears cellular debris and pathogens from the body.
"The vacuum-cleaner cell presents the allergen or antigen to the immune system in a way that says, 'No worries, this belongs here,'" Miller said. "The immune system then shuts down its attack on the allergen, and the immune system is reset to normal."
There currently is no treatment for coeliac disease.
In the coeliac disease trial, the nanoparticle was loaded with gliadin, the major component of dietary gluten, found in cereal grains such as wheat. A week after treatment, the patients were fed gluten for 14 days. Without treatment, coeliac patients eating gluten developed marked immune responses to gliadin and damage in their small intestine.
Coeliac patients treated with the COUR nanoparticle, CNP-101, showed 90% less immune inflammation response than untreated patients. By stopping the inflammatory response, CNP-101 showed the capacity to protect the intestines from gluten related injury.
"Doctors can only prescribe gluten avoidance, which is not always effective and carries a heavy social and economic toll for coeliac patients," Miller said.
About 1% of the population has coeliac disease, a serious autoimmune disease in which the ingestion of gluten leads to damage in the small intestine. When people with coeliac disease eat gluten (a protein found in wheat), their body mounts an immune response that attacks the small intestine.
Autoimmune diseases generally can only be treated with immune suppressants that provide some relief, but undermine the immune system and lead to toxic side-effects. CNP-101 does not suppress the immune system but reverses the course of disease.
"Coeliac disease is unlike many other autoimmune disorders because the offending antigen (environmental trigger) is well known - gluten in the diet," said Dr. Ciaran Kelly, professor of medicine at Harvard Medical School and director of the Celiac Center at Beth Israel Deaconess Medical Center. "This makes coeliac disease a perfect condition to address using this exciting nanoparticle induced immune tolerance approach."