(Sabine Schulte, Pixabay)
22 Oct. 2019. Results from a clinical trial show an experimental treatment encourages immune-system tolerance of gluten, preventing intestinal damage from celiac disease. Researchers from Northwestern University and COUR Pharmaceutical Development Company are presenting their findings today at the European Gastroenterology Week conference in Barcelona, with Takeda Pharmaecuticals licensing the therapy in a deal valued at $420 million.
Celiac disease is an inherited autoimmune disorder, where the body’s immune system reacts to gluten, a protein found in wheat, rye, and barley. The immune reaction destroys the nutrient absorption capacity of the small intestine, leading to tissue damage. About 1 percent of people worldwide have celiac disease, with the only protection against symptoms being a strict gluten-free diet.
Stephen Miller, a professor of immunology and microbiology at Northwestern University’s medical school in Chicago studies the mechanisms behind autoimmune diseases, allergies, and immune reactions, and develops new processes for countering those conditions. Among the techniques studied by Miller and colleagues is the formulation of treatments using nanoscale biodegradable particles to disguise offending antigen protein or allergen, and allow the immune system to accept the substances.
In this case, the nanoparticles are made of poly lactic-co-glycolic acid or PLGA, a biocompatible and biodegradable polymer often used in medical devices and for drug delivery. The particles contain tiny amounts of gliadin proteins found in gluten, but are seen as non-offending in the blood stream and ingested by macrophages — white blood cells in the immune system that take in foreign matter — to accept the particles without causing a reaction.
Macrophages ingest foreign matter like vacuum cleaner cells, but also use a non-inflammatory pathway in the body to dispose of their contents. “The vacuum-cleaner cell presents the allergen or antigen to the immune system in a way that says, ‘No worries, this belongs here,’” says Miller in a university statement. “The immune system then shuts down its attack on the allergen, and the immune system is reset to normal.”
The mid-stage clinical trial enrolled 34 adults with celiac disease to test the treatment code-named CNP-101. Participants were randomly assigned to receive two intravenous treatments of CNP-101 seven days apart, or a placebo. One week later, participants were given 12 grams of gluten per day for three days, then six grams of gluten a day for 11 more days. The study team looked primarily for production of immune reaction proteins, before and after activating T-cells in the immune system react to the gluten.
The results show participants receiving CNP-101 have lower releases of immune-system proteins than placebo recipients, with the differences large enough for statistical reliability. In addition, participants receiving CNP-101 have less damage to mucous layers in their small intestines than placebo recipients. Six participants had to discontinue the trial from reactions to the gluten challenge, but no serious adverse effects were reported. Other adverse effects, such as nausea, diarrhea, and headache experienced by both CNP-101 and placebo recipients, say the researchers, were mild and temporary.
As reported by Science & Enterprise in April 2016, COUR Pharmaceutical in Chicago licenses the nanoparticle technology from Northwestern University, and developed CNP-101 through its early stages. Takeda Pharmaceuticals in Osaka, Japan earlier agreed to a deal with COUR for CNP-101, giving Takeda a future option to fully license the treatment from COUR.
Based on the trial results, Takeda and COUR are moving ahead with the licensing agreement, giving Takeda the rights to CNP-101 — renamed TAK-101 by Takeda — in exchange for future milestone and royalty payments that could reach $420 million if all facets of the deal are fulfilled. For the next step, Takeda plans to launch a study of TAK-101 to determine optimum doses of the treatment.
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