Researchers at the University of Alberta have discovered a unique process of brain cell death that affects the cells that are most vulnerable in multiple sclerosis (MS).
After identifying the process called pyroptosis, or fiery death, the researchers were able to block the enzyme in the brain that is responsible for it, using a drug that could potentially treat MS.
Commenting on the findings, Chris Power, a Neurologist, lead Author of the study and Co-director of the UAlberta MS Centre told the University of Alberta: “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 is already known to be safe in humans.”
The study, titled ‘Capase-1 inhibition prevents glial inflammasome activation and pryoptosis in models of multiple sclerosis’ was published in Proceedings of the National Academy of Science of the United States of America and 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. Importantly, researchers were able to show pyroptosis in both brain tissues from MS patients and in lab models of MS.
Researchers found that the drug known as VX-765 protected oligodendrocytes, the cells that insulate nerves in the brain and are susceptible to damage in MS. VX-765 is currently in clinical trials for epilepsy.
“We think this drug would break the cycle of neurotoxic inflammation and thus prevent future loss of brain cell in MS,” said Brienne McKenzie, first Author on the study and a PhD student in the U of A’s Faculty of Medicine & Dentistry.
The research team believe identifying this mechanism also opens the doors to new indicators for monitoring disease progression of MS.
“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.”