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slon [soylentnews.org] writes:

An investigational treatment for celiac disease effectively controls the condition—at least in an animal model—in a first-of-its-kind therapeutic for a condition that affects approximately 70 million people worldwide.

Currently, there is no treatment for celiac disease, which is caused by dietary exposure to gluten, a protein in wheat, barley and rye. The grains can produce severe intestinal symptoms, leading to inflammation and bloating.

Indeed, celiac disease is the bane of bread and pasta lovers around the world, and despite fastidiously maintaining a gluten-free eating plan, the disease can still lead to social isolation and poor nutrition, gastroenterologists say. It is a serious autoimmune disorder that, when left unaddressed, can cause malnutrition, bone loss, anemia, and elevated cancer risk, primarily intestinal lymphoma.

Now, an international team of scientists led by researchers in Switzerland hope to change the fate of celiac patients for the better. A series of innovative experiments has produced "a cell soothing" technique that targets regulatory T cells, the immune system components commonly known as Tregs.

The cell-based technique borrows from a form of cancer therapy and underlies a unique discovery that may eventually lead to a new treatment strategy, data in the study suggests.

"Celiac disease is a chronic inflammatory disorder of the small intestine with a global prevalence of about 1%," writes Dr. Raphaël Porret, lead author of the research published in Science Translational Medicine.

"The condition is caused by a maladapted immune response to cereal gluten proteins, which causes tissue damage in the gut and the formation of autoantibodies to the enzyme transglutaminase," continued Porret, a researcher in the department of Immunology and Allergy at the University of Lausanne.

Working with colleagues from the University of California, San Francisco, as well as at the Norwegian Celiac Disease Research Center at the University of Oslo, Porret and colleagues have advanced a novel concept. They theorize that a form of cell therapy, based on a breakthrough form of cancer treatment, might also work against celiac disease.

In an animal model, Porret and his global team of researchers have tested the equivalent of CAR T cell therapy against celiac disease. The team acknowledged that the "T_reg contribution to the natural history of celiac disease is still controversial," but the researchers also demonstrated that at least in their animal model of human celiac disease, the treatment worked.

CAR T cell therapy is a type of cancer immunotherapy in which a patient's T cells are genetically modified in the laboratory to recognize and kill cancer cells. The cells are then infused back into the patient to provide a round-the-clock form of cancer treatment. In the case of celiac disease, the T cells are modified to affect the activity of T cells that become hyperactive in the presence of gluten.

To make this work, the researchers had to know every aspect of the immune response against gluten. "Celiac disease, a gluten-sensitive enteropathy, demonstrates a strong human leukocyte antigen association, with more than 90% of patients carrying the HLA-DQ2.5 allotype," Porret wrote, describing the human leukocyte antigen profile of most patients with celiac disease.

As a novel treatment against the condition, the team engineered effector T cells and regulatory T cells and successfully tested them in their animal model. Scientists infused these cells together into mice and evaluated the regulatory T cells' ability to quiet the effector T cells response to gluten. They observed that oral exposure to gluten caused the effector cells to flock to the intestines when they were infused without the engineered T_regs.

However, the engineered regulatory T cells prevented this gut migration and suppressed the effector T cells' proliferation in response to gluten. Although this is a first step, the promising early results indicate that cell therapy approaches could one day lead to a long-sought treatment for this debilitating intestinal disorder.

"Our study paves the way for a better understanding of key antigen-activating steps after dietary antigen [gluten] uptake," Porret concluded. "Although further work is needed to assess T_reg efficacy in the setting of an active disease, our study provides proof-of-concept evidence that engineered T_regs hold therapeutic potential for restoring gluten tolerance in patients with celiac disease."

Original Submission