Could protecting the axon represent a promising treatment strategy for ALS?
Collaborators: Dr. Gary Armstrong, McGill University
Dr. Alex Parker, at the Centre de recherche du CHUM, Université de Montreal, is one of the first two recipients of the newly introduced three-year, $300,000 ALS Canada–Brain Canada Discovery Grant. Dr. Parker’s grant was funded in generous partnership with Dr. Jean-Pierre Canuel Fund – SLA Québec.
Dr. Parker’s project looks at possible targets for slowing neuronal degeneration in small worms used to model ALS, called C. elegans, which he has worked with since his days as a doctoral student at the University of British Columbia. He has been fascinated by neurodegeneration even as an early career researcher.
“I liked the idea of trying to model neurodegeneration in a simple system,” he says. “You can go fast and find things.”
He started his work looking at Huntington’s Disease before switching to ALS – a challenging disease that motivates him to work on problems not everyone wants to tackle.
“ALS is not like other diseases. It’s a hard problem – the disease window is short and aggressive,” says Dr. Parker. “For many people, it seems intractable. But we’re keeping at it – and I think we can make a contribution.”
For decades, researchers have used worm models to understand which genes help regrow neuronal axons after they are damaged. To date, these genes have not been studied for their role in the damage done by ALS.
Dr. Parker began this project by cataloging more than 100 of these genes – which either promote axonal regrowth or slow further damage – as potential targets for study in ALS models.
“We tested them all. And lo and behold, some of them actually stopped further neurodegeneration in an ALS model,” he says.
He then tested his “short list” on older worms that better simulate the cellular environment of ALS patients, who tend to be diagnosed in midlife or later. The result was two “extremely potent targets for slowing neurodegeneration,” he notes.
“We’re taking biology that’s known and rephrasing it for ALS,” Dr. Parker explains. The hope is to find drugs that can target these genetic pathways that reignite a cell’s ability to regenerate its own axons, effectively slowing disease progression.
He said the upgraded funding opportunity helped him think more ambitiously about the project and bring in collaborators that could accelerate the research.
Dr. Parker is working with Dr. Gary Armstrong at McGill University, an expert on zebrafish models. With the larger funding amount, Dr. Parker can move his hypothesis through different levels of validation, including zebrafish and iPSCs (human cell models), which could allow him to advance his findings to clinical trial on a much shorter timeline.
“The structure of the grant opened up the possibility of pushing this further and faster,” he says. “We’re already moving towards validation, and we just started.”
“This type of program is so important,” he adds. “It funds projects at the early stages, when it’s more challenging to get funding. This ALS Canada-Brain Canada Discovery Grant gave us the chance to really get our research going.”
Supporting research at its earliest stages leads to transformative breakthroughs that have a lasting impact on human health and well-being. By funding early-stage research, we can address critical gaps in knowledge, focus on emerging challenges, and encourage researchers to explore unconventional approaches.”Dr. Viviane Poupon, President and CEO of Brain Canada
The ALS Canada-Brain Canada Discovery Grant Program has been made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada), Brain Canada Foundation and ALS Canada.
To find out more about the 2022 ALS Canada-Brain Canada Discovery Grants, read the full press release here.