New anti-inflammatory molecule could halt MS progression

March 17, 2015

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).

Dr Ueli Nachbur, Associate Professor John Silke, Associate Professor Guillaume Lessene, Professor Andrew Lew and colleagues developed the molecule inhibit 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 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."

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. Nevertheless, this delay is enough to completely shut off cytokine production," he said.

"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."
-end-
The research was published today 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.

Walter and Eliza Hall Institute

Related Multiple Sclerosis Articles from Brightsurf:

New therapy improves treatment for multiple sclerosis
A new therapy that binds a cytokine to a blood protein shows potential in treating multiple sclerosis, and may even prevent it.

'Reelin' in a new treatment for multiple sclerosis
In an animal model of multiple sclerosis (MS), decreasing the amount of a protein made in the liver significantly protected against development of the disease's characteristic symptoms and promoted recovery in symptomatic animals, UTSW scientists report.

Not all multiple sclerosis-like diseases are alike
Scientists say some myelin-damaging disorders have a distinctive pathology that groups them into a unique disease entity.

New therapeutic options for multiple sclerosis in sight
Strategies for treating multiple sclerosis have so far focused primarily on T and B cells.

Diet has an impact on the multiple sclerosis disease course
The short-chain fatty acid propionic acid influences the intestine-mediated immune regulation in people with multiple sclerosis (MS).

The gut may be involved in the development of multiple sclerosis
It is incompletely understood which factors in patients with multiple sclerosis act as a trigger for the immune system to attack the brain and spinal cord.

Slowing the progression of multiple sclerosis
Over 77,000 Canadians are living with multiple sclerosis, a disease whose causes still remain unknown.

7T MRI offers new insights into multiple sclerosis
Investigators from Brigham and Women's Hospital have completed a new study using 7 Tesla (7T) MRI -- a far more powerful imaging technology -- to further examine LME in MS patients

How to improve multiple sclerosis therapy
Medications currently used to treat multiple sclerosis (MS) can merely reduce relapses during the initial relapsing-remitting phase.

Vaccinations not a risk factor for multiple sclerosis
Data from over 12,000 multiple sclerosis (MS) patients formed the basis of a study by the Technical University of Munich (TUM) which investigated the population's vaccination behavior in relation to MS.

Read More: Multiple Sclerosis News and Multiple Sclerosis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.