US Pharm. 2019;44(12):5.
Findings of a new phase II clinical study using technology developed at Northwestern University predict that it is possible to induce immune tolerance to gluten in people suffering from celiac disease. The findings might enable celiac patients to eventually tolerate gluten in their diets.
Following treatment, patients were able to eat gluten with a significant reduction in inflammation. The results also indicate that the technology protected patients’ small intestine against gluten exposure. The clinical findings were presented October 22 at the European Gastroenterology Week conference in Barcelona, Spain. The technology is a biodegradable nanoparticle containing gluten that instructs the body’s immune system that the antigen is safe. In effect, the nanoparticle behaves like a Trojan horse, hiding the antigen in a friendly shell.
The finding by Northwestern scientists lays the groundwork for the technology, developed in the laboratory of Stephen Miller, professor of microbiology and immunology at Northwestern University Feinberg School of Medicine, to potentially treat other diseases and allergies, such as multiple sclerosis, type 1 diabetes, peanut allergy, asthma, and more.
“This is the first demonstration the technology works in patients,” said Dr. Miller. “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 injected into the bloodstream, patients’ immune systems interpret the allergen-loaded nanoparticle as innocuous debris. The nanoparticle and its concealed cargo are consumed by a macrophage, a “vacuum-cleaner” cell that clears cellular debris and pathogens. “The immune system then shuts down its attack on the allergen, and the immune system is reset to normal,” said Dr. Miller.
In the celiac-disease trial, the nanoparticle was loaded with gliadin, the major component of dietary gluten. A week later, the patients were fed gluten for 14 days. Without treatment, celiac patients eating gluten developed marked immune responses to gliadin and damage in their small intestine. In contrast, celiac patients treated with the COUR nanoparticle, CNP-101, showed 90% less immune inflammation response. By stopping the inflammatory response, CNP-101 showed the capacity to protect the intestines from gluten-related injury. (The nanotechnology was licensed to COUR Pharmaceuticals Co., a biotechnology company cofounded by Dr. Miller.)
Approximately 1% of the population has celiac disease, a serious autoimmune disorder with no currently available treatment in which the ingestion of gluten leads to small-intestine damage upon activation of patients’ immune systems.
Customarily, autoimmune diseases are treated with suppressants that provide relief but undermine the immune system. CNP-101 does not suppress the immune system, but instead reverses the course of disease.
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