Australian researchers develop new anti-inflammatory molecule that could help treat MS
18th March, 2015
Walter and Eliza Hall Institute (WEHI) scientists have developed a new drug-like molecule that can halt inflammation and has shown promise in stopping an MS-like illness in mice.
Dr Ueli Nachbur, Associate Professor John Silke, Associate Professor Guillaume Lessene, Professor Andrew Lew and their colleagues have collaborated to develop the molecule, which inhibits a key signal that triggers inflammation.
The research has been published in the prestigious journal Nature Communications. During inflammation, the cells of the immune system release chemicals called cytokines, which stimulate other cells of the immune system to respond to the ‘threat’. In MS, the immune response is mistakenly directed at the tissues of the central nervous system - brain, spinal cord and optic nerves – causing damage that leads to neurological symptoms such as blurred vision, sensory changes, paralysis, pain and thinking and memory changes.
In an effort to stop this immune response, the research team at the Walter and Eliza Hall Institute have 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.
Drug-like molecules that target RIPK2 have been developed in the past, but in this instance the researchers were able to produce a drug that is exceptionally specific for RIP2K and does not affect the activity of any other similar molecules. Such specificity is very important in drug development as it helps to ensure that medications are carefully targeted at the disease process while reducing potential unwanted side-effects.
The team conducted a very thorough series of experiments using WEHI-345 and were able to show that the drug could block the release of both human and mouse cytokines in cells grown in the laboratory. WEHI-345 was also able to block the release of cytokines in mice in response to bacteria or similar stimuli.
Most importantly, the team treated mice with the MS-like illness Experimental Autoimmune Encephalitis (EAE) after the illness had started, and found that the drug could greatly reduce the symptoms of the disease in these mice. In fact, in 50% of the mice the disease process was stopped completely.
Associate Professor Lessene, at the Walter and Eliza Hall Institute said, '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.'
The team will now work on refining the drug-like molecule and conduct further experiments to understand the way the inflammatory signalling pathway works as well as working towards developing this molecule as a potential treatment for inflammatory diseases, such as MS.
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.