New anti-inflammatory molecule could halt MS progression

AUSTRALIAN scientists 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 from the Walter and Eliza Hall Institute developed the molecule, which inhibits a key signal that triggers inflammation.

Multiple sclerosis 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 were 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 signalling protein called RIPK2. This prevents the release of inflammatory cytokines.

Professor Lew said the research team 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.”

Associate Professor Lessene, who developed the molecule with colleagues in the institute’s ACRF Chemical Biology division, said WEHI-345 had potential as an anti-inflammatory agent.

“This molecule will be a great starting point for a drug-discovery program that may one day lead to new treatments for MS and other inflammatory diseases,” Associate Professor Lessene said.

Dr Nachbur said institute scientists would use WEHI-345 to further investigate the signalling pathway that produced inflammatory cytokines and to develop a better, stronger inhibitor of RIPK2 for treating inflammatory disease. “This signalling pathway must be finely balanced, because WEHI-345 only delayed signalling rather than blocked it,” Dr Nachbur said. “Nevertheless, this delay is enough to completely shut off cytokine production.

“Not only is this a potential new treatment, it is a great tool we can use to unravel this signalling pathway and identify other important proteins that control inflammation that could be a drug target.”

The research will be published in the journal Nature Communications. The study was funded by the Australian National Health and Medical Research Council, the Swiss National Science Foundation, the Australian Research Council and the Victorian Government.

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Ryan Fritz

Ryan Fritz started The Advocate in 2014 to provide not-for-profits and charities with another media platform to tell their worthwhile hard news stories and opinion pieces effortlessly. In 2020, Ryan formed a team of volunteer journalists to help spread even more high-quality stories from the third sector. He also has over 10 years of experience as a media and communications professional for not-for-profits and charities.

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