Nature study led by Keenan scientist shows ‘new take’ on a cell involved in Multiple Sclerosis

Dr. Veronique Miron

A cell previously seen as an instigator of damage in neurological diseases like Multiple Sclerosis (MS) may actually help to protect the nervous system.

Myelin acts as insulation that surrounds nerve fibres in the central nervous system, and is damaged through aging and in diseases like MS. In a study published in Nature, Dr. Veronique Miron, a scientist at the Keenan Research Centre for Biomedical Science, and her team found that a cell in the central nervous system, called the microglia, prevents myelin from degenerating by secreting a molecule called TGF-beta.

Microglia was previously seen as a cause of damage in the nervous system rather than a protector, and this discovery could shed light on treatments for diseases that cause damage to myelin.

Unity Health is home to Canada’s largest clinic for people with MS, providing world-class specialty care for patients and leading research and innovation. Drawn to this bold focus and the Keenan Research Centre’s integration to clinical care, Miron joined Unity Health’s research team this year as the second foundational scientist focused on MS. She is also the John David Eaton Chair in Multiple Sclerosis Research at the BARLO Multiple Sclerosis Centre. We met with Miron to learn more about her recent study and her goals for research in this area.

What did you discover through this work?

Miron: We’re interested in myelin, which is critical for nerve health and function. With aging and many neurodegenerative diseases, myelin starts to grow in excess and then degenerates, causing problems in nerve function, like cognitive impairment. We don’t yet understand the mechanisms that control the health of myelin and prevent degeneration.

In this study we found that a central nervous system resident immune cell called the microglia is required to prevent myelin from growing in excess and prevent myelin from degenerating. We found it does this through secreting a molecule called TGF-beta. This molecule acts on the cells that make the myelin, which are called oligodendrocytes. The TGF-beta is released by the microglia, it’s taken up by the oligodendrocytes, and that limits their myelin growth and it prevents the myelin from degenerating so it’s really important in maintaining the health of myelin.

This means microglia are needed to preserve myelin health, and that when they’re missing, then you have myelin degeneration.

Myelin is often impacted in neurodegenerative diseases like MS. How do you hope that this discovery leads to an impact for patients in this field?

Miron: In terms of immediate implications for patients with a neurological condition, we showed in the paper that there’s a rare disorder called adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), in which patients have less of these microglia in the brain. We found that was associated with this myelin damage. Our discoveries in terms of how microglia support myelin health in the immediate future could be useful for people with ALSP.

Looking at the bigger picture of how this could apply to, for example, MS, we were really surprised, but excited to see that without microglia, you get this myelin degeneration because we know that in MS the myelin degenerates, but it’s not fully understood how this happens.

What do you hope that people will do with this new knowledge?

Miron: This study shows that microglia are really important players in supporting the health of myelin. We hope that this highlights them as a therapeutic target in developing new strategies to try to support central nervous system health in these different conditions.

We’re seeing it as a study that highlights the importance of this cell in maintaining the health of the central nervous system, which is a new take on it because this cell was often implicated in causing damage in the central nervous system. This is probably also the case, but I think what’s quite important is that we’ve shown that they’re not just sitting around waiting to become detrimental, but rather they do have these important protective function in maintaining the health.

What’s next for this research?

Miron: This study has led us to think that with disease and aging, there may be something wrong with the microglia, as if they’re not even there. Could it be they’re making less TGF-Beta and that’s why we see these problems with myelin and problems with the central nervous system?

With MS, in areas where there isn’t yet damage, there are these little clusters of microglia that are called nodules, and people think that this is likely where the lesion is going to start forming. That fits into our hypothesis that there may be dysregulated microglia in these areas of the brain in MS and they could potentially initiate the myelin damage in that area. That’s another thing we want to look at.

You recently joined Unity Health. What drew you to our research institute and what are you most excited about?

A big draw for me was coming to a place where translating findings from the bench to the bedside, real interactions between clinicians and scientists, and more integration into the hospital setting is an important mission and strategy as it is at Unity Health Toronto.

It’s exciting to be able to integrate into one of the world-leading centres in MS research and really have the opportunity to integrate into the clinical setting quite easily as the framework is there.

How does having foundational and basic scientists focusing on an area of world-class specialty care at Unity Health really strengthen our ability to help the patients living with the disease?

There’s still so much we don’t understand about MS. We need to be able to understand fundamental mechanisms that regulate the disease or different aspects of the disease in order to feed that through to drug discovery and treatment.

It goes both ways here, we have access to samples from patients coming through the clinic, and that informs our research. If we have this hypothesis that these cells might be involved in myelin repair, we can easily look at these cells in people with MS and profile them and see how they’re different. If we have a patient progressing, or doing better, we can use that to inform our research and identify new therapeutic strategies, to hopefully promote myelin health and repair.

By: Ana Gajic