Thomas Simmen (left) and Yohannes Haile are co-authors of a study pinpointing a possible culprit for multiple sclerosis. Their research opens new avenues for treating the debilitating disease.
In the relentless battle against multiple sclerosis (MS), University of Alberta researchers recently discovered an entirely new cellular mechanism—an underlying defect in brain cells—that may be to blame for the disease, and a potential hallmark that may be a target for future treatment.
The finding opens the door to a brand new avenue of study in the battle against the cryptic autoimmune disorder that strikes more Canadians than any other nationality worldwide, said U of A neurologist Fabrizio Giuliani, medical director of the Northern Alberta MS Clinic and co-author of the study.
“Scientists have been pointing to the mitochondria, the powerhouse of the cell, as a possible link to MS but have not been able to decipher how they malfunction. Ours is the first study that combines clinical and lab experiments to explain how mitochondria become defective in MS patients,” said Thomas Simmen, a cell biology researcher and co-author on the study.
Using human brain tissue samples, post-doctoral fellow Yohannes Haile discovered how two sub-components within a cell are miscommunicating in patients with MS, and identified how at least one protein, Rab32, is swooping in to trigger the dangerous dysfunction.
“A part of the cell that stores calcium (endoplasmic reticulum or ER) gets too close to the part of the cell that creates energy (mitochondria) when massive amounts of Rab32 are present in the brain of MS patients. The resulting miscommunication with the calcium supply triggers the mitochondria to misbehave, ultimately causing toxicity for brain cells in MS patients,” explained Simmen.
In healthy brain tissue samples, there’s virtually no Rab32 present, he added.
Researchers don’t know what causes an unwelcome influx of Rab32 but they theorize the defect could originate at the base of the ER.
With this finding in hand, scientists can now search for effective treatments that target Rab32 and embark on determining whether there are other proteins that may be at play, added Simmen.
“Rab32 is just one of the proteins that is having the effect of drawing the ER and mitochondria too close. There are dozens of other possibilities,” he said.
This discovery may give hope to the 100,000 Canadians living with MS who have had to rely on treatments that have proven only partially effective.
The study, conducted with researchers at the University of Exeter, was recently published in the Journal of Neuroinflammation.