Anti-inflammatory molecule could treat MS

Anti-inflammatory molecule could treat MS

Virally infected cells
June 2015

Associate Professor Guillaume Lessene, Professor Andrew Lew and Dr Ueli Nachbur
Associate Professor Guillaume Lessene, Professor Andrew Lew,
Dr Ueli Nachbur (L-R) and colleagues developed a new drug-like
molecule that halts progression of multiple sclerosis.

Walter and Eliza Hall Institute scientists have developed a new drug-like molecule that can halt inflammation and has shown promise in preventing the progression of multiple sclerosis (MS).

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.

Dr Ueli Nachbur, Associate Professor John Silke, Associate Professor Guillaume LesseneProfessor Andrew Lew and colleagues developed the molecule to inhibit a key signal that triggers inflammation.

Reducing collateral damage

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, which is a hallmark 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 that attack and damage tissues in autoimmune diseases.

Professor Lew said the team examined WEHI-345’s potential to treat MS in experimental models of the disease.

“We treated preclinical models with WEHI-345 after symptoms of disease first appeared, and found WEHI-345 could prevent further progression of MS in 50 per cent of cases,” he said. “These results are extremely important, as there are currently no good preventive treatments for MS.”

Developing new treatments

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 develop a better, stronger inhibitor of RIPK2 for treating inflammatory disease. “Not only is this a potential new treatment, it is a great tool to unravel this signalling pathway and identify other important proteins that control inflammation that could be a drug target,” Dr Nachbur said.