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Possible new target for treatment of multiple sclerosis

A host of possibilities just opened up for treating the mysterious, pervasive illness

Date:
March 23, 2017
Source:
University of Alberta Faculty of Medicine & Dentistry
Summary:
In the relentless battle against multiple sclerosis (MS), researchers recently discovered an entirely new cellular mechanism -- an underlying defect in brain cells -- that may to be blame for the disease, and a potential hallmark that may be a target for future treatment.
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In the relentless battle against multiple sclerosis (MS), U of A researchers recently discovered an entirely new cellular mechanism -- an underlying defect in brain cells -- that may to be 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 Fabrizio Giuliani, study co-author, U of A neurologist and medical director of the Northern Alberta MS Clinic.

"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, study co-author and cell biology professor.

Specifically, using human brain tissue samples, the researchers 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 (ER or endoplasmic reticulum) 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 why or 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, not only can scientists search for effective treatments that target Rab32, added Simmen, they can embark on determining whether there are other proteins that may be at play.

"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 partially effective treatments that aim to reduce inflammation, and, sometimes, controversial experiential treatments such as the vein-widening treatment.

The study, conducted with researchers at the University of Exeter, was recently published in the Journal of Neuroinflammation.


Story Source:

Materials provided by University of Alberta Faculty of Medicine & Dentistry. Original written by Lesley Young. Note: Content may be edited for style and length.


Journal Reference:

  1. Yohannes Haile, Xiaodan Deng, Carolina Ortiz-Sandoval, Nasser Tahbaz, Aleksandra Janowicz, Jian-Qiang Lu, Bradley J. Kerr, Nicholas J. Gutowski, Janet E. Holley, Paul Eggleton, Fabrizio Giuliani, Thomas Simmen. Rab32 connects ER stress to mitochondrial defects in multiple sclerosis. Journal of Neuroinflammation, 2017; 14 (1) DOI: 10.1186/s12974-016-0788-z

Cite This Page:

University of Alberta Faculty of Medicine & Dentistry. "Possible new target for treatment of multiple sclerosis: A host of possibilities just opened up for treating the mysterious, pervasive illness." ScienceDaily. ScienceDaily, 23 March 2017. <www.sciencedaily.com/releases/2017/03/170323125508.htm>.
University of Alberta Faculty of Medicine & Dentistry. (2017, March 23). Possible new target for treatment of multiple sclerosis: A host of possibilities just opened up for treating the mysterious, pervasive illness. ScienceDaily. Retrieved May 29, 2017 from www.sciencedaily.com/releases/2017/03/170323125508.htm
University of Alberta Faculty of Medicine & Dentistry. "Possible new target for treatment of multiple sclerosis: A host of possibilities just opened up for treating the mysterious, pervasive illness." ScienceDaily. www.sciencedaily.com/releases/2017/03/170323125508.htm (accessed May 29, 2017).

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