Neurologist Christopher Power and PhD student Brienne McKenzie discovered a fundamental mechanism that causes brain cell damage in people with MS. Photo by: Melissa Fabrizio.
While discovering a process in the brain causing cell death that occurs in multiple sclerosis, researchers at the University of Alberta may have also found a way to treat the disease.
Neurologist Chris Power and his team identified pyroptosis, or fiery death. 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.
To identify pyroptosis, the team discovered an enzyme that is responsible for the process. They found that a drug called VX-765 blocked the enzyme and protected oligodendrocytes, the cells that insulate nerves in the brain. These cells are highly susceptible to damage in MS.
"We think this drug would break the cycle of neurotoxic inflammation and thus prevent future loss of brain cells in MS," said Brienne McKenzie, first author on the study and a PhD student in the U of A's Faculty of Medicine & Dentistry.
"Existing MS treatments work to reduce inflammation, but there is nothing that targets the brain cells themselves," said 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."
The discovery also opens doors to new biomarkers or indicators for monitoring disease progression of MS, which has been challenging since symptoms can vary widely between patients with MS.
VX-765 is already known to be safe in humans.
The study, published in PNAS, was a collaboration with the National Institutes of Health in Washington, D.C. The MS Society of Canada and the University Hospital Foundation provided funding support.