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Molecules show promise against autoinflammatory diseases

By Allen Cone
Molecules show promise against autoinflammatory diseases
Researchers found two small molecule combinations are offering promise for treatment of autoinflammatory diseases, including psoriasis. Photo by Hans/pixabay

July 5 (UPI) -- Two small molecule combinations have shown potential for treating autoinflammatory diseases in a recent study in Switzerland.

Researchers at the Federal Institute of Technology in Lausanne, Switzerland, found the new combinations effectively block a central pathway of the innate immune system. Their findings were published Wednesday in the journal Nature.

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There are more than 100 autoimmune diseases, including Addison's, celiac, Chrohn's, Fibromyalgia, juvenile arthritis, lupus, lyme, multiple sclerosis, narcolepsy, psoriasis, rheumatic fever, type 1 diabetes, Graves' and ulcerative colitis, according to the American Autoimmune Related Diseases Association.

The first-in-class compounds studied in Switzerland specifically activate a protein called STING -- STimulator of Interferon Genes -- that help cells fight off the infecting pathogen. Small molecules are low in molecular weight and up to a nanometer in size.

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"Our work uncovered an unexpected mechanism to target STING and provided the first proof-of-concept that anti-STING therapies are efficacious in autoinflammatory disease," Dr. Andrea Ablasser, a researcher at the school in Switzerland, said in a press release.

The innate immune system, as the body's first line of defense, attacks threats like viruses and bacteria. The cells use receptors that can identify microbial DNA and in turn activate STING.

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However, the immune system can cause autoinflammatory diseases by turning against the body.

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So far, researchers have not developed drugs that act on specific molecules.

The researchers in Switzerland looked for molecules that can suppress STING proteins.

To find which ones ones block STING, the researchers mutated amino acids in protein found in human and mouse cells. They discovered a protein that attaches a fatty acid to STING, which when activated, is assembled into multiple clusters.

The researchers then tested the effect of the compounds on actual autoinflammatory diseases in mice, finding that treatment with either compound class significantly reduced key pathogenic features in mice.

"Beyond specific monogenic autoinflammatory syndromes, the innate immune system is implicated in even broader 'inflammatory' conditions, so we are excited to learn more about the role of STING in human diseases," Ablasser said.

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