A strain of probiotic will soon be tested as a potential treatment for amyotrophic lateral sclerosis (ALS).
The clinical study is taking place thanks to a $1.6 million investment by the Weston Family Foundation – an investment that builds on a series of Discovery Grants from ALS Canada and Brain Canada.
“This trial has received a lot of interest from people around the world. And I completely understand why – ALS is a devastating, incurable disease,” explains Dr. Alex Parker, lead investigator and neuroscientist based at the CHUM Research Centre (CRCHUM) in Montreal. “Probiotics are well-known. And they’re not drugs, so the risk of side effects is minimal. We’re in the early stages of this trial, and there’s a lot of work to do, but we’re hopeful.”
Dr. Parker and his team use animal models to better understand – and ultimately find solutions for – diseases like ALS. Driven by trainee turned research associate Dr. Audrey Labarre, who recently received a Mitacs Accelerate internship to support her work, they discovered that a specific probiotic bacteria called Lacticaseibacillus rhamnosus HA-114 protects motor neurons in worm models of ALS. Motor neurons are the nerve cells that wire the brain and control muscular movement.
With a 2021 Discovery Grant from ALS Canada and Brain Canada, Dr. Parker and his team confirmed that the same protective effect occurs with a more complex animal model, the mouse. They were also able to bring on two key collaborators to help better understand the biological mechanisms behind the effect – Dr. Martine Tétreault, a bioinformatics specialist at the CRCHUM, and Dr. Matthieu Ruiz, a lipids specialist at the Université de Montréal and co-director of the metabolomics platform at the Montreal Heart Institute.
Using genetic, behavioural, and imaging analyses, the team identified that lipid metabolism – and specifically the process of beta-oxidation that breaks lipids down into energy in the body’s cells – is impaired in ALS and restored with the probiotic. They believe that the HA-114 probiotic achieves this restoration by supplying lipids to the energy powerhouse of the cell, the mitochondria. The boosted lipid supply rebalances energy metabolism in ALS and leads to a decrease in neurodegeneration.
This evidence of lipids playing a role in the mechanism of ALS provides a new direction for biomarker discovery. Because lipids are present in blood and serum samples, using lipids as a biomarker would offer a relatively easy, non-invasive way of testing patients to diagnose the disease, monitor an individual’s disease progression, and assess their response to treatment.
“This work has been supported by ALS Canada and Brain Canada Discovery Grants all along at different stages. Other funders just didn’t quite get what we were doing at the time,” says Dr. Parker. One of the main goals of the Discovery Grant program is to enable the researcher to get the preliminary data they need to obtain a bigger grant.
“It’s an important program – it really accelerates research and allows people to get going,” he explains.
The clinical study of the HA-114 probiotic will be led by CHUM ALS clinic director Dr. Geneviève Matte and involve 100 Canadian participants. Using serum and blood samples, the team will study the lipids and microbiomes of participants before and after treatment with the probiotic. Comparing healthy people and those with ALS will allow the team to better understand the lipid profile of ALS patients. It will also allow them to determine whether the restorative effects they’ve seen in worm and mouse models is possible in humans.
Future work in Dr. Parker’s laboratory will also involve testing the HA-114 probiotic in other models of neurodegenerative disease.
“So far, the probiotic works in a lot of the worm models involving misfolded proteins, including Huntington’s disease and Alzheimer’s disease, but not all,” he explains. “So we’re asking ourselves, ‘what’s going on here’? We have a lot of work to do, but you know – that’s the way research works.”
An important caveat to this story: the HA-114 probiotic under study is not yet commercially available. Anyone considering taking probiotic supplements for ALS or any other neurodegenerative disease should consult their doctor or specialist.