Results of a new phase 2 clinical trial using technology developed at
Northwestern Medicine show it is possible to induce immune tolerance to gluten
in individuals with celiac disease. The findings may pave the way for treated
celiac patients to eventually tolerate gluten in their diet.
After treatment with the technology, the patients were able to eat gluten
with a substantial reduction in inflammation. The results also show a trend
toward protecting patients’ small intestine from gluten exposure.
The findings will be presented as a late-breaking presentation Oct. 22 at
the European Gastroenterology Week conference in Barcelona, Spain.
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.
Beyond celiac 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
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.”
In the celiac 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,
celiac patients eating gluten developed marked immune responses to gliadin and
damage in their small intestine.
Celiac 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.
There currently is no treatment for celiac disease.
“Doctors can only prescribe gluten avoidance, which is not always effective
and carries a heavy social and economic toll for celiac patients,” Miller said.
About 1% of the population has celiac disease, a serious
autoimmune disease in which the ingestion of gluten leads to damage
in the small intestine. When people with celiac 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.
“Celiac 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 celiac disease a perfect condition to address using this exciting
nanoparticle induced immune tolerance approach.”
Kelly, who will be presenting the research abstract in Barcelona, has been
working with Miller to apply the technology and define the therapeutic approach
to treating celiac disease.
What is Celiac
Disease?
Celiac disease is a serious autoimmune disease that occurs in genetically
predisposed people where the ingestion of gluten leads to damage in the small
intestine. It is estimated to affect 1 in 100 people worldwide. Two and
one-half million Americans are undiagnosed and are at risk for long-term health
complications.
When people with celiac disease eat gluten (a protein found in wheat, rye
and barley), their body mounts an immune response that attacks the small
intestine. These attacks lead to damage on the villi, small fingerlike
projections that line the small intestine, that promote nutrient absorption.
When the villi get damaged, nutrients cannot be absorbed properly into the
body.
Celiac disease is hereditary, meaning that it runs in families. People
with a first-degree relative with celiac disease (parent, child, sibling) have
a 1 in 10 risk of developing celiac disease.
Celiac disease can develop at any age after people start eating foods or
medicines that contain gluten. Left untreated, celiac disease can lead to
additional serious health problems.
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