Multiple sclerosis: potential risk factors, cognitive impairment and the microbiome

Written by Sharon Salt, Editor

Marianna Cortese (MD, PhD) is a postdoctoral fellow at the Harvard School of Public Health (MA, USA) and is working in the research group of Dr Alberto Ascherio and Dr Kassandra Munger (both Harvard University). Marianna is currently focusing on multiple sclerosis (MS), including new potential risk factors of MS and cognitive impairment.
In this interview, Marianna speaks to us about her talk on vitamin D, smoking, Epstein–Barr virus (EBV) and long-term cognitive performance in clinically isolated syndrome (CIS) patients: an 11-year follow-up study of the BENEFIT trial. She also discusses how the microbiome might play a role in disease etiology by mediating the effects of MS risk factors.
What inspired you to work in this area?

I’m always struck to see how young MS patients are and how they’re taken out in the middle of their lives; when they’re trying to establish themselves professionally and privately. All of a sudden they get a disease that is so unpredictable. It sounds very hard and it would be nice to be able to prevent it one day.

You’ve presented a talk at ECTRIMS on vitamin D, smoking, EBV and long-term cognitive performance – could you give us an overview of this?

To summarize, what we saw in the data is that those with higher vitamin D in the first years do better cognitively at year 11 and those that smoke in the first years do worse.”

My talk was on the potential predictors of cognitive impairment. Cognitive impairment is a very serious and common problem in MS – up to 70% of patients will develop cognitive impairment. We wanted to explore whether the established risk factors of MS (i.e., low vitamin D, smoking and EBV infection) have anything to say for the development of cognitive dysfunction during the disease course.

We had this unique possibility to work on the BENEFIT data, which was a clinical trial approximately 15 years ago, where investigators wanted to assess whether early treatment with interferon β-1b of CIS patients – so individuals with neurologic symptoms that suggest MS and are at high risk of developing the disease – would have some sort of advantage. For example, whether these patients were less likely to develop MS. They treated these patients for 2 years where some received treatment right away and others did not. Long-term outcome was also assessed by the researchers and luckily, we were able to have the BENEFIT 11 dataset. This is an 11-year follow-up of these patients to look at long-term cognitive function.

To summarize, what we saw in the data is that those with higher vitamin D in the first years do better cognitively at year 11 and those that smoke in the first years do worse. EBV infection didn’t seem to have a lot to say for cognitive impairment. We were eager to assess these exposures right after disease manifestation and cognitive function 11 years later, so long apart, to minimize the risk that the disease progression itself influenced – whether they had low vitamin D etc. 

In your opinion, what are the key challenges to overcome in this field?

The key challenge I think is related to neurodegeneration in MS – cognitive impairment is a sign of neurodegenerative disease and we just don’t have good options today to treat that or slow it down. We’re very good at tackling neuroinflammation but not degeneration. Cognitive impairment would definitely be an area to investigate further, as it affects patients so much. They can fall out of employment and it impairs their quality of life, so if we could prevent or slow it down, we would be reaching a lot.

How do you think these challenges can be overcome?

That’s a good question. Of course, one area is to look at treatment options to find drugs that are effective against neurodegeneration. Another field I’m very fond of is prevention, which is the field I’m currently working in; to find factors that we can modify where we can intervene early when the patient shows first signs of MS and then we could prevent some of them to worsen cognitively.

What further investigations do you have planned for this area of research?

For cognitive impairment, we will have to see. We are still working on this data and we’re also going to look at radiological and clinical outcomes to have the bigger picture. We are also planning to look more into the development of neurodegeneration from the very beginning of the disease and how it relates to inflammation in the brain that causes the disabling attacks in MS. Is it an independent process or does one trigger the other? What comes first? If we understand what happens, we are more likely to find a treatment or preventive factors.

More broadly, where do you hope the field will be in 5–10 years’ time?

If I can hope for it, we will have understood the mechanisms of neurodegeneration better because that’s what would really make a difference for the patient from today’s perspective. Ideally, that we can prevent MS; that we can somehow eradicate it – but that’s a very idealistic and hopeful outlook.

I read on your institutional biography about how you’re interested in possibly looking at the microbiome and its relationship with MS. Could you tell us more about this?

Somehow, the features of the twin with MS were maybe transferred to the mouse, as they developed autoimmune diseases more often than mice that got the microbiome of the twin without MS.”

Around 2–3 years ago, I heard about the microbiome research in MS for the first time. I found it quite intriguing because it made so much sense to me. Everything we know today about MS, the risk factors, they somehow influence the microbiome and I was wondering whether the microbiome could mediate these effects on a molecular level. There has been a lot of interest in the microbiome and many autoimmune diseases, so it was definitely an area to look into for MS.

What was very intriguing to me was that Professor Wekerle (Max Planck Institute of Neurobiology, Munich, Germany) and his research group did a study on monozygotic twins, where one had MS and the other did not; they transplanted fecal samples of these twins into mice that had been genetically modified to spontaneously develop an autoimmune disease in the brain. Somehow, the features of the twin with MS were maybe transferred to the mouse, as they developed autoimmune diseases more often than mice that got the microbiome of the twin without MS.

People are starting to collect stool samples to do more research and we’re only at the very beginning stages of this research area. It’s a very exciting field but we’re only just about to understand what a normal microbiome is and whatnot, as this depends on so many factors such as nutrition, life factors, smoking, travelling, etc.

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The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Neuro Central or Future Science Group.