canadian labs leading the way in multiple sclerosis research
two canadian researchers are hot on the trail of better therapies for ms patients, which include a protein already existing in the brain and a better understanding of the gut-brain connection.
6 minute read
canada has one of the highest ms rates in the world, impacting one in every 400 people.
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what if your brain could regenerate through medication — or even, the foods that you eat?
there’s a very real possibility and promise in canadian laboratory work as scientists are leading new research to reverse the effects of multiple sclerosis and other neurodegenerative diseases.
multiple sclerosis (ms) is an autoimmune disease where the fatty, protective lining of nerve cells, known as myelin, is eroded. this leads to nerve damage, slowing and disrupting the signalling between the brain and the body. one of the challenges for patients and their families is that ms symptoms can be unpredictable, including blurred vision, weakness, impaired sensation, memory problems and paralysis.
while there are treatments and advances in detection, the causes of ms are not really understood and nothing exists to reverse the disease process.
canada has one of the highest ms rates in the world with more than 90,000 living with the disease — one in every 400 people — according to ms canada. patients are an average of 43 years old, however, it can also be diagnosed in children and teens. while the majority are initially diagnosed with the relapsing-remitting form of ms (where disease progression is followed by periods of little to no symptoms), about 10 per cent have more progressive ms that steadily gets worse.
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brain molecule may halt and even reverse the effects of multiple sclerosis
“we used to think our brain is just what it is and that’s all you have for the rest of your life,” says anastassia voronova, university of alberta researcher and assistant professor in medical genetics, and the canada research chair in neural stem cell biology. “but now we know it’s a fluid organ that has limited potential to self-repair. figuring out how to boost that self-repair and how to make it work for us is where we need to go.”
voronova says one of the fundamental questions in neurobiology is how neural stem cells build and repair the brain — it’s a question she’s applied to ms, one of her specialties, and recently discovered how a specific brain molecule can halt and even reverse the effects of ms.
in her research published in stem cell reports, voronova and her team injected fractalkine, a protein commonly found in the brain, into mice with chemically induced ms. the treatment increased the number of new oligodendrocytes, the brain and spinal cord cells that produce myelin.
“if we can replace those lost or damaged oligodendrocytes, then they could make new myelin and it is believed that would halt the disease progression, or maybe even reverse some of the symptoms,” voronova says. other researchers have shown that fractalkine may protect nerves in mice before disease, but this is the first testing on mice who have ms.
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during the study, voronova says her team also saw a reduction in brain inflammation caused by the autoimmune response. this, too, could demonstrate the associated boost in self-repair from the fractalkine injection.
with the critical funding support of ms canada, voronova says she is moving forward with her work to understand how to use medications to activate these vital stem cells in the brain.
“my mom definitely told me, ‘don’t stress out too much. the nerve cells don’t regenerate,’ which was the prevailing theory. now we know that that’s not true,” she says.
“we also know that we do have these stem cells in our adult brain that have a very limited capacity to replace the damaged or lost brain cells, including oligodendrocytes. the problem is that this process is highly inefficient, especially in people with multiple sclerosis. but it also offers a lot of hope.”
gut microbiome could play a role in ms
jennifer gommerman, immunologist and tier 1 canada research chair in tissue specific immunity, is another leader in ms research who is looking at the gut microbiome, the community of microbes that lives in the gut, and how it can influence immune function and neuroinflammation in brain disease like ms. her lab at the university of toronto, where she is a professor of immunology, has developed an animal model that represents the disease pathology in the brains of people with ms to identify microbiomes that promote brain injury.
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“we know that there are genes that are associated with the risk of getting the disease,” gommerman says. “if someone with ms has an identical twin, that twin will have about a 30 per cent chance of getting ms, so that [genetic] risk is not 100 per cent.”
“that means that the environment plays a big role in the risk of developing ms.”
gommerman explains research in the field of immunology points to the microbiome “as a window into our environmental exposure.” for example, if a person switches to a high-fibre diet, the microbiome will adapt to that high-fibre diet and it will become different from someone who eats a low-fibre diet.
environmental exposure also includes lifestyle choices like exercise, alcohol consumption and sleep quality that change the microbiome. the underlying thought is that the microbiome itself reflects the environment. ms researchers want to better understand the microbiome to learn about strategies, such as diet, to reduce the risk of disease.
gommerman’s efforts, also supported by ms canada, are looking at potential therapies that address the progressive phase of the disease and how it unfolds.
“a lot of ms patients will progress in their disease as they age, but not everyone does. we are hypothesizing that this could be linked to the microbiome, which talks to the immune system, and can even come directly to the brain through these mediators called metabolites,” gommerman says.
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she credits the collaborative work of colleagues in canada and abroad for the advanced therapies that can quiet the inflammatory part of ms for people diagnosed in their 20s or 30s. they typically have the relapsing form of the disease where symptoms like muscle spasms, stiffness, weakness and fatigue can subside for periods at a time.
“although it’s not perfect, there are good ways to treat these patients who respond pretty well, but we don’t have good therapies that deal with the progressive phase of the disease.”
could eating certain foods potentially slow the disease in progressive ms?
it’s too early to say for sure if a change in diet can slow disease progression, but we do know the microbiome can be modified by environmental inputs like food.
“in theory, you can alter a microbial community by changing your diet, but we don’t know what that would look like,” she says. “the hope is that there’s something that we can modify, and those metabolites i mentioned are also druggable targets.”
the outcome of her research could be the beginning of an effective drug therapy for progressive ms. she’s also linked to the barlo ms centre at st. michael’s hospital in toronto which has joined an international consortium to examine how the microbiome differs in ms patients.
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“the immune system is an incredibly potent, powerful weapon,” she says of the dysregulated immune response in progressive ms. “ … we really need to better understand what those immune cells are doing in the brain, who are the good guys, who are the bad guys, and be smart about how to treat that. and that’s a much bigger puzzle.”
as voronova says, the long hours in the lab are important to drive research forward and help patients. “i am very hopeful investigations like these will ultimately lead to some kind of therapy, whether it’s a pill or an injection or something else that is going to be brought forward to people with ms who desperately need it.”
karen hawthorne is a toronto-based writer.
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