New Molecule Targets RIPK1 to Inhibits Cytokine Production and Halt Inflammation; Shows Initial Potential for Preventing MS Progression in Model Systems

Walter and Eliza Hall Institute scientists in Australia have developed a new drug-like molecule that can halt inflammation and has shown promise in preventing the progression of multiple sclerosis (MS). Dr. Ueli Nachbur, Associate Professor John Silke, Associate Professor Guillaume Lessene, Professor Andrew Lew, and colleagues developed the molecule to inhibit a key signal that triggers inflammation. Multiple sclerosis (MS) is an inflammatory disease that damages the central nervous system, including the brain, spinal cord, and optic nerves. There is no cure and there is a desperate need for new and better treatments. Inflammatory diseases such as MS are triggered by an over-active immune system, Dr. Nachbur said. "Inflammation results when our immune cells release hormones called cytokines, which is a normal response to disease," he said. "However, when too many cytokines are produced, inflammation can get out-of-control and damage our own body, all of which are hallmarks of immune or inflammatory diseases." To apply the brakes on this runaway immune response, institute researchers developed a small drug-like molecule called WEHI-345 that binds to and inhibits a key immune signaling protein called RIPK2 (receptor-interacting serine/threonine-protein kinase 2). This prevents the release of inflammatory cytokines. Professor Lew said they examined WEHI-345's potential to treat immune diseases in experimental models of MS. "We treated preclinical models with WEHI-345 after symptoms of MS first appeared, and found it could prevent further progression of the disease in 50 per cent of cases," he said. "These results are extremely important, as there are currently no good preventive treatments for MS." The article was published online on March 17, 2015 in Nature Communications.
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