A new study out of McMaster University suggests that common viral infections — like influenza or COVID-19 — may accelerate the onset and progression of amyotrophic lateral sclerosis, or ALS.
While viral infections have long been associated with neurodegenerative diseases, it has been unclear how infections caused by very diverse viruses all seem to increase risk. The new findings — published today in the journal Nature Communications — suggest that it is the immune response triggered by these infections that accelerates the onset and progression of ALS.
"ALS is a debilitating and incurable disease, so it's critical that we improve our understanding of the common environmental factors that can hasten its onset and accelerate its progression," says Matthew Miller, a professor of Biochemistry and Biomedical Sciences at McMaster and principal investigator on the new study. "Understanding what triggers or accelerates the disease could illuminate new strategies for slowing or even stopping it."
Commonly known as Lou Gehrig's disease, ALS is the most common motor neuron disease, affecting about one in 300 Canadians . ALS progressively damages the nerve cells responsible for mobility, ultimately leading to severe weakness, paralysis, and death. With no known cure, researchers are working to better understand the key factors that contribute to the disease, so that new treatment options can be explored.
Researchers in Miller's lab monitored animal models of ALS following infection with either influenza A virus or SARS-CoV-2, the virus that causes COVID-19. They then compared these models to a cohort of uninfected animals and observed that the animals that experienced infection also experienced a much more rapid decline in motor function.
Imran Ahmed, a master's student working in Miller's lab, says the research team took a novel approach to the study, focusing not only on the potential connections between infections and ALS, but also on why infections might influence disease progression in the first place.
"A lot of the previous work in this area has been epidemiological in nature, without much focus on the molecular mechanisms that actually underpin the connection between infections and ALS," says Ahmed, who co-first authored the new paper with Miller Lab alumni Art Marzok and Jonathan Mapletoft. "What makes our study unique is that we did take a mechanistic approach — we explored why this connection might exist."
What the researchers found was that even common respiratory viruses that do not infect neurons can leave lasting changes to the nervous system.
In their animal models, Miller's team observed that COVID-19 and flu infections triggered an inflammatory response from immune cells in the nervous system — a process called gliosis — that remained elevated in the spinal cord even after the virus had been cleared from the body. Gliosis, Ahmed notes, is already known to play an important role in ALS, but the findings suggest that an infection may amplify this process, helping to accelerate the disease.
For Marzok, who completed both a PhD and a postdoctoral fellowship in Miller's lab, one of the most striking details about the new findings is the fact that a single infection could prompt elevated gliosis, or scar tissue, in the spine.
"In our pre-clinical models, just one viral infection was enough to significantly accelerate ALS progression, even after the infection itself had resolved," says Marzok. "These findings strongly suggest that viral infections — and the inflammatory responses that they trigger — may fundamentally influence the course of the disease."
Miller, who is scientific director of the Michael G. DeGroote Institute for Infectious Disease Research and executive director of NexusHealth , says that the findings point to potential therapeutic interventions for delaying the onset and slowing the progression of ALS in lieu of an actual cure.
In fact, during this study, his team treated infections with antivirals and supressed gliosis with anti-inflammatories, and in both cases saw a significant reduction in the rate of ALS progression.
"Developing better vaccines and antiviral therapies — and improving the public's trust in them — could have health benefits that we don't fully appreciate," says Miller. "Our work here suggests that preventing or limiting common infections could at the same time protect your nervous system from the damage that accelerates ALS."
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