UofA discovers a fiery process that may attribute to cell death in MS patients

by • June 29, 2018 • Feature Slider, Feature-Home, Featured-Slides-Home, UncategorizedComments Off on UofA discovers a fiery process that may attribute to cell death in MS patients188

Neurologist Christopher Power and Ph.D. student Brienne McKenzie discovered a fundamental mechanism that causes brain cell damage in people with MS. (Photo: Melissa Fabrizio)

MS is an extremely debilitating disease that has record diagnosis levels in Alberta that pose questions to researchers and a drive to stop it in its tracks. Scientists from the University of Alberta while discovering a method of cell death that affects the cells most vulnerable in multiple sclerosis, may have stumbled across a drug that could potentially treat this incurable and misunderstood disease.

Chris Power, a neurologist from the University of Alberta and his team identified pyroptosis – fiery death – by using the drug VX-765 that blocks the enzyme in the brain responsible for the process.

They discovered that the drug protects oligodendrocytes, which are the cells that insulate nerves in the brain and are susceptible to damage in MS. VX-765 is also currently in clinical trials for treating epilepsy.

“We think this drug would break the cycle of neurotoxic inflammation and thus prevent future loss of brain cells in MS,” says Brienne McKenzie, first author on the study and a Ph.D. student in the U of A’s Faculty of Medicine & Dentistry.

Power and his team believe identifying this mechanism may also open the doors to new indicators for monitoring disease progression of MS, which is a challenge in itself as symptoms can vary widely between patients.

“Existing MS treatments work to reduce inflammation, but there is nothing that targets the brain cells themselves,” says Avindra Nath, clinical director of the National Institute of Neurological Disorder and Stroke at the National Institutes of Health in Bethesda, MD. “This paper identifies a clinically relevant novel pathway that opens the doors to new therapeutic targets that prevent cell damage.”

Power, co-director of the UAlberta MS Centre, adds that, “This could be a game changer, because we discovered a fundamental mechanism by which brain cells are damaged in MS that couples inflammation with neurodegeneration. The drug, VX-765, is already known to be safe in humans.”

MS is classified as an autoimmune disease of the central nervous system that attacks the myelin sheath that protects the nerves. It often comes on anywhere from adolescence to age 40 with causes unknown. On average 11 people are diagnosed daily or 1 in every 385 Canadians.

The study marks the first molecular analysis of pyroptosis in the human brain. Pyroptosis is a type of programmed cell death that is associated with inflammation, but its role in MS was previously unknown. Power’s lab was able to show pyroptosis in both brain tissues from MS patients and in lab models of MS.

“The study’s findings make a key contribution to the MS field in identifying a novel mechanism that contributes to progression in MS,” says Karen Lee, vice-president of research at the MS Society of Canada. “The MS Society of Canada is encouraged by the results of this study and what it means for people living with MS—hope for another avenue through which treatment options can be explored to stop MS in its tracks.”

The study was a collaboration with a laboratory at the National Institutes of Health in Washington, D.C. The MS Society of Canada and the University Hospital Foundation provided funding support for the research.

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