Autoimmune Disease Discovery Could Spark New Treatments; Scientists Synthesize Small Molecule Inhibitor of Toll-Like Receptor 8 (TLR8)

University of Colorado (UC) Boulder researchers have discovered a potent, drug-like compound that could someday revolutionize treatment of rheumatoid arthritis and other autoimmune diseases by inhibiting a protein instrumental in prompting the body to start attacking its own tissue. "We have discovered a key to lock this protein in a resting state," said Dr. Hang Hubert Yin, a biochemistry professor at the BioFrontiers Institute and lead author of a paper, published on November 20, 2017 in Nature Chemical Biology, describing the discovery. "This could be paradigm shifting." The article is titled “Small-Molecule Inhibition of TLR8 Through Stabilization of Its Resting State.” More than 23.5 million Americans suffer from autoimmune diseases like rheumatoid arthritis, scleroderma, and lupus, in which an excessive immune response leads to pain, inflammation, skin disorders, and other chronic health problems. Three of the top five selling drugs in the United States aim to ease autoimmune disease symptoms. But no cure exists, and treatments are expensive and come with side effects. "Given the prevalence of these diseases, there is a big push for alternatives," Dr. Yin said. For years, scientists have suspected that a protein called Toll-like receptor 8 (TLR8) plays a key role in the innate immune response. When TLR8 senses the presence of a virus or bacterium, it goes through a series of steps to transform from its passive to active state, triggering a cascade of inflammatory signals to fight off the foreign invader. But, as Dr. Yin explained, "it can be a double-edged sword" leading to disease when that response is excessive.
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