Thinking outside the box

Probiotics are friendly, live bacteria that are good for the digestive system. You may be familiar with the digestive benefits of probiotics in foods like yogurt or kefir. Many scientists are investigating how changes in the composition of intestinal bacteria may play a role in a range of diseases including obesity, colorectal cancer, cardiovascular disease and ALS.

Three years ago, doctoral student Audrey Labarre was feeding probiotics to tiny worms called C. elegans in the lab of Dr. Alex Parker at the Research Centre of the University Hospital of Montreal (CRCHUM). The worms are only a millimetre long, but since they have short lifespans and share 60 per cent of their genetic makeup with humans, they are ideal animals to use in research. Labarre was investigating whether different probiotic strains would have an impact on how the worms accumulated fat.

At the same time, but in a separate project, Labarre was researching motor neuron degeneration in worms that had been genetically modified with human genes associated with ALS — TDP-43 and FUS. One day, she decided to see what would happen if she fed probiotics from her other project to the ALS worms. Her curiosity paid off with an important new insight. “I was surprised that one of the 20 probiotic strains I tested not only decreased fat accumulation, it completely rescued paralysis and motor neuron death in the ALS worms,” said Labarre.

In 2016, under an ALS Canada-Brain Canada Discovery Grant awarded to Dr. Alex Parker, she continued her research and successfully identified the underlying biological processes that explain how the probiotics play a protective role in worms with ALS.

Labarre recently received a $75,000 Trainee Award from ALS Canada to advance her surprising discoveries through the next stage of research to see if she can find the same effects in mice. With this grant, she will feed probiotics to ALS mice and measure disease onset and lifespan. She will also analyze their brains and spinal cords to examine if and how the most promising probiotic strain known as “strain number 7” may affect motor neuron degeneration.

“I hope to find a similar effect with probiotics in mice,” said Labarre, “while keeping in mind that in worms, we can study the impact of a single bacteria at a time. Mice have a larger and much more diverse set of intestinal bacteria, so there are more factors to consider.” Mice are closer to humans in genetic makeup than worms. In general, the areas of DNA responsible for coding proteins in mice are about 60 to 85 identical to those found in humans.

“With science, there are plenty of new ideas, like stones in the field. I like to find ideas off the beaten path,” she said. “I’m very excited about my project. A few years ago, researchers who suggested that intestinal bacteria can have a massive effect on the nervous system were not taken seriously. I’m lucky because I stuck to my research question and my hypothesis is supported by a lot of data now.”

Labarre is energized by ALS as a field of study. “It’s the only one I know where all the researchers, people with ALS, caregivers and doctors are so interested in all that we do,” she said. “I have been to many of the ALS Canada Research Forums held each year in May, and every time I’m amazed at how hard people are working to find new ways to help people living with ALS.”

ALS Canada has been supporting world-class research across Canada for more than 30 years with a variety of grants and awards with the goal of making ALS a treatable, not a terminal condition. ALS Canada Trainee Awards support Canada’s emerging ALS researchers, whether they are doctoral students, post-doctoral researchers, or clinical research fellows. Trainee awards encourage young researchers to choose ALS as their area of focus, helping to ensure that Canada has a strong talent base today and into the future.

This research project is one of 12 funded by the ALS Canada Research Program in 2017 following a rigorous scientific assessment by panels of global ALS experts. The panellists evaluated a larger pool of applications to identify the projects that are grounded in scientific excellence and have the potential to most quickly advance the field of ALS research in order to develop effective treatments.

ALS Canada is a registered charity that receives no government funding. Everything we do – from funding research to providing community-based support for people living with ALS – is possible only because of donor generosity and partnerships with provincial ALS Societies who contribute to the ALS Canada Research Program.

Watch this video of Audrey Labarre talk about some of her other research.

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Posted in: Research