U of M team finds a key to ALS

November 1, 2013
Author: Larry Kusch

University of Manitoba researchers have made a breakthrough in explaining how a certain mutated gene causes ALS, sparking hope a treatment can soon be found to slow the debilitating and fatal disease's progress.

Their discovery, reported Thursday in the journal PLOS Genetics, found the mutated gene TLS/FUS creates a "runaway train" effect that produces too much protein within cells.
'I'll be first in line (for any new treatment),' says Winnipegger Victor Perrin, a former elementary school principal who was diagnosed with ALS in January 2008.

'I'll be first in line (for any new treatment),' says Winnipegger Victor Perrin, a former elementary school principal who was diagnosed with ALS in January 2008.

What is ALS?

Amyotrophic lateral sclerosis is a fatal, rapidly progressive neuromuscular disease that affects about 260 Manitobans and 3,000 people across Canada. It attacks voluntary muscles such as those in the arms, legs and chest. Death usually occurs when the chest muscles are no longer able to help the lungs operate adequately.

Is there a cure?

No, not yet. Nor is there any standard treatment for slowing the disease's progress.

What did U of M researchers discover?

They've published a theory of how the disease operates, opening the way for the development of a future treatment that could at least slow its progression.

There is currently no cure for amyotrophic lateral sclerosis -- also known as Lou Gehrig's disease after the famous baseball player who was diagnosed with the disease in the late 1930s. As many as 80 per cent of those who get it lose their lives within two to five years of diagnosis.

Dr. Geoff Hicks, who led the research, had studied the gene for a decade, mainly in relation to cancer, before making the discovery.
Ruth Bonneville / Winnipeg Free Press

'I'll be first in line (for any new treatment),' says Winnipegger Victor Perrin, a former elementary school principal who was diagnosed with ALS in January 2008.

He and his team of grad students and fellows at the Manitoba Institute of Cell Biology and the U of M's regenerative medicine program, are also working on a drug that could one day slow the progress of the disease.

That news was greeted with enthusiasm by the ALS Society of Manitoba and a local sufferer.

"I'll be first in line (for any new treatment)," said Victor Perrin, a former Winnipeg elementary school principal who was diagnosed with ALS in January 2008.

Perrin, 58, said Thursday he is "completely dependent" on other people for his care, having lost all muscle strength in his limbs. His breathing has also been affected.

He said it's "quite exciting" important research is occurring in his own province. "You basically live day to day with the hope that -- if not for myself maybe for the next generation -- there will be a cure. And it starts with these kinds of discoveries that they just made at the University of Manitoba," he said in an interview.

About 3,000 Canadians -- 260 in Manitoba -- are afflicted with the rapidly progressive neuromuscular disease.

Diana Rasmussen, executive director of the ALS Society of Manitoba, said the organization is excited about the discovery and is seeking to learn more about it.

"Anything that comes out that's going to enhance the lifespan and quality of life for people living with ALS is great," she said Thursday.

Hicks and his team found when healthy cells make enough TLS protein, some of it travels back into the nucleus to tell the cell to stop making more of it. This auto-regulation controls how much is being made so the cell doesn't make too much.

In people with ALS, a genetic mutation prevents the protein from travelling back into the nucleus so the cell keeps producing more and more.

"In the context of the ALS disease, you have this runaway-train situation, because you're continuously making more of this protein, which is harmful to the cell," Hicks said.

The extra proteins build up in the cell in large clumps, disrupting normal cell function and leading to muscle problems.

Hicks also said the TLS mutations play a role in cancer, so the team's research has broader implications than for just ALS.

"It really is a breakthrough. It's revealing a new direction that can really be chased down to find new avenues (of treating disease)," he said.

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"Anything that comes out that's going to enhance the lifespan and quality of life for people living with ALS is great," Diana Rasmussen, executive director of the ALS Society of Manitoba said Thursday.