Could this new treatment really reverse celiac disease?

via Northwestern University Feinberg School of Medicine

New technology may be applicable to other autoimmune diseases and allergies

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. Thenanoparticle 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.

The nanotechnology was licensed to COUR Pharmaceuticals Co., a biotech based in Northbrook and co-founded by Miller. COUR developed CNP-101, which was granted Fast Track status from the U.S. Food and Drug Administration, and brought the therapy to patients in collaboration with Takeda Pharmaceuticals. Takeda will announce Tuesday they have acquired an exclusive global license to develop and commercialize this investigational medicine for celiac disease.

“Given the license by Takeda, COUR will focus on clinical programs in peanut allergy and multiple sclerosis in the near term and broaden even further over time,” said John J. Puisis, president and chief executive officer of COUR.

Learn more: New treatment may reverse celiac disease

 

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A cure for celiac disease by 2021?

In an industrial collaboration project, TU Wien has developed a medication that can alleviate or even completely eliminate the symptoms of celiac disease. It should be available as early as 2021.

Celiac disease is a fairly common disease, affecting one to two percent of the European population. It is expressed as a hypersensitivity to gluten, a protein found in cereals such as wheat, barley or rye.

Although efforts are already being made to treat celiac disease, the proposed drugs have an effect on the immune system. Possible side effects must therefore be examined very carefully. Although initial clinical studies are underway, they will not lead to a marketable product in the next few years.

For this reason, an entirely different approach has been pursued at TU Wien in collaboration with the industrial partner Sciotech Diagnostic Technologies GmbH. Instead of developing a drug that interferes with the immune system, TU Wien has created a simple medical product that directly attacks the gluten molecules to render them harmless. This makes the approval process much simpler, meaning that the product should be available in ordinary pharmacies as early as 2021.

Molecules like keys and locks

“Our bodies produce antibodies that fit intruding antigens precisely, like a key to a lock. This immune response makes these antigens harmless,” explains Professor Oliver Spadiut, head of the Integrated Bioprocess Development Research Group at TU Wien. “If a new antibody fragment is found and produced that docks to and blocks the invading gluten molecule without triggering the immune system, the symptoms of celiac disease can be suppressed.”

The aim of the research project was therefore to produce a complex of two such antibody fragments that envelop the gluten molecule at a molecular level, so that it can no longer have any further effects in the intestines.

To do this, certain bacteria have to be reprogrammed so that they produce exactly the desired antibody fragment. “The formation of such proteins in a bacterium is a highly complicated process,” explains Oliver Spadiut. “It can easily happen that the proteins are not folded exactly as we want.” Instead of the desired antibody fragments, so-called “inclusion bodies” are formed – small particles consisting of incorrectly folded proteins. A process therefore had to be developed to refold these inclusion bodies and to obtain the desired proteins from them.

Such processes, in which the folding of proteins is specifically altered, have not yet been studied in great detail and so they are not very efficient. “You have to precisely understand the chemical processes involved and intervene in a complicated way,” says Oliver Spadiut. “It has therefore taken a while, but we have now developed a process that can be easily reproduced, can be scaled up to industrial application and delivers a very good yield of the desired product”

In pharmacies soon

The project was supported by the industrial partner SCIOTEC Diagnostic Technologies GmbH, who will now bring the new medical product to the market. “It will be a preparation that celiac patients can take together with gluten-containing foods to alleviate coeliac symptoms,” explains Oliver Spadiut. “It remains to be seen whether the symptoms will disappear completely or will only be alleviated. The precise effects will probably vary from person to person.

Learn more: A new remedy for celiac disease

 

 

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