{"id":3427,"date":"2022-04-01T00:55:57","date_gmt":"2022-04-01T00:55:57","guid":{"rendered":"https:\/\/linksus.net\/the-future-of-multiple-sclerosis-medical-news-today\/"},"modified":"2022-04-01T00:55:57","modified_gmt":"2022-04-01T00:55:57","slug":"the-future-of-multiple-sclerosis-medical-news-today","status":"publish","type":"post","link":"https:\/\/linksus2.linksus.net\/index.php\/2022\/04\/01\/the-future-of-multiple-sclerosis-medical-news-today\/","title":{"rendered":"The future of multiple sclerosis – Medical News Today"},"content":{"rendered":"

Millions of people worldwide live with multiple sclerosis (MS), a life-altering, progressive condition. What is the likely cause of MS, and how is medical research advancing towards better treatments? We explore these questions and more in our latest In Conversation podcast.
Multiple sclerosis means \u201cmany scars.\u201d It is a chronic condition that mainly affects the central nervous system<\/a>, where the protective sheath of nerves in the brain, spinal cord, and optic nerves, called \u201cmyelin,\u201d slowly degrades.
More recently, evidence<\/a> is also emerging of some involvement of the peripheral nervous system<\/a><\/hl-trusted-source> in the development of this condition.
The symptoms<\/a> of MS vary widely among people and range from blurred vision, numbness, and tingling in the limbs to progressive disease that can lead to paralysis.
There is no cure for MS, but there are drugs<\/a> that can alter the course of the condition.
Research in recent years has determined a few things about risk factors<\/a>. For example, low levels of vitamin D<\/a>, smoking, having overweight, and living farther from the Equator can increase the risk. Moreover, MS affects around three times as many women as men. <\/strong>
Perhaps most intriguingly, some research<\/a> has found a link between MS and infection with the Epstein-Barr virus (EBV). This is the virus that causes mononucleosis<\/a>, or \u201cmono,\u201d sometimes also known as \u201cglandular fever<\/a>.\u201d
Earlier this year, the strongest evidence yet that EBV may cause appeared in the scientific journal Science<\/a><\/em>.
In our latest In Conversation<\/a> podcast, we spoke with Dr. Antje Ronneberger, a 53-year-old family doctor from Devon, United Kingdom, who recently retired due to her MS diagnosis. We also spoke with Dr. Marianna Cortese<\/a>, research associate at Harvard T.H. Chan School of Public Health in Boston, and co-author of the Science<\/em> paper arguing that EBV infection could be a likely cause of MS.
This article provides an edited and shortened record of Medical News Today\u2019s<\/em> In Conversation <\/em>podcast about MS. We have added reference links to key research findings mentioned in the podcast. Please listen to the podcast \u2014 below or on your preferred platform \u2014 for the full discussion.
Dr. Hilary Guite: Antje, how did you know you had MS?<\/strong>
Dr. Antje Ronneberger:<\/strong> That\u2019s a very difficult question because it took a long time [to receive a diagnosis]. Although I\u2019m a doctor myself, who sometimes has to do with an MS diagnosis, I didn\u2019t know I had MS. I just felt there was something wrong. I was incredibly fatigued. That was probably my first symptom. But as you know, all doctors work very hard, especially family doctors in the U.K. I worked far too long, for too many hours, and put it down to that.
So I thought I had burnout<\/a> rather than anything else. Then my next symptom was probably mobility problems, balance problems, that kind of thing. I became clumsy and incredibly slow. So those were probably the first symptoms.
And then, what is very unusual for MS is that I lost a lot of weight, about 20 kilos, which is not the rule at all, and didn\u2019t make you think of MS. But that happened to me, not sure why.
Maybe it was the stress<\/a>, but that\u2019s what brought me to see my doctor and have investigations because I couldn\u2019t stop the weight loss.
Dr. Marianna Cortese: <\/strong>How long did it take you to be diagnosed? It must have been very difficult, the wait and uncertainty.
Dr. Ronneberger<\/strong>: I probably had some symptoms for about 10 years, or maybe even 20, my neurologist thinks, because I had balance problems for a short period of time 20 years ago. But let\u2019s say 5 years, it became more and more significant [over the last] 5 years.
Dr. Guite: You had a brain scan<\/a>, that was the thing that sealed the diagnosis<\/a> because there\u2019s so much overlap with the symptoms with all sorts of other things. How did you get to the point of getting a brain scan?<\/strong>
Dr. Ronneberger<\/strong>: <\/strong>Well, I think the fatigue<\/a> was one reason. The other thing was that I had a certain weakness in my right leg, which was only there if I walked for a while and I tripped over my right foot. So I do have a foot drop<\/a> now. That sort of became slowly apparent. And that\u2019s why my family doctor requested an MRI scan<\/a> of my spinal cord.
Only after that he referred me to the neurologist who asked for a brain scan of my head as well because he didn\u2019t suspect MS. The first neurologist \u2014 all my examinations by him were actually normal. And then I had the brain scan, and he phoned me a few days later and said it looks like demyelination and MS. So that\u2019s how it came about.
Dr. Guite: Myelin is the protective sheath that covers nerve fibers. So demyelination<\/a>, do either of you want to explain what that actually means what it looks like on the scan?<\/strong>
Dr. <\/strong>Cortese<\/strong>: What happens in MS is that the immune system attacks the myelin sheath around the neurons in the central nervous system, and this myelin sheath breaks down.
This can affect the signal transmission of the nerve and also makes the nerve more vulnerable to damage since this myelin sheath is really there for the insulation and protection of the neuron. This can lead to an array of different symptoms, as Antje was describing.
Dr. Guite: There are different types of MS, aren\u2019t there? There\u2019s a type that\u2019s progressive, and then a type where people have attacks with remissions and may even actually go back almost to normal. What type do you have, Antje?<\/strong>
Dr. Ronneberger<\/strong>:<\/strong><\/strong>I\u2019ve got the remitting relapsing form.<\/a>
Dr. Guite: So that\u2019s the most common, isn\u2019t it? It\u2019s about 85% of people <\/a>who have that. What brings the attacks on? Is this sudden, you suddenly get what, like blurred vision or dizziness? <\/strong>
Dr. Ronneberger<\/strong>:<\/strong><\/strong> [My relapses] are very, very subtle. That\u2019s why it took so long to diagnose [my MS]. What brings them on? Not sure.
Actually, I was going to ask Marianna if she\u2019s got any more research in that way. But they say it could be stress, it could be tiredness, and viral infections, as any virus makes it worse and especially fatigue. Sleep deprivation is another thing.
Dr. <\/strong>Cortese<\/strong>: <\/strong>Unfortunately, ultimately, it\u2019s not well understood. This is something we\u2019re also currently studying<\/a> in our group \u2014 whether they are markers that could help us predict whether someone will have a more severe disease course, more attacks, but it\u2019s ultimately not well understood.
And that\u2019s also something that patients struggle with when they get a diagnosis in the middle of their lives. It\u2019s not clear who will have a more benign course and a more severe course.
And this could also help to select more adequate treatments, more potent treatments if the disease will go more severely. But you know, more potent treatments can have more side effects. So this is a very relevant question that the community is investigating, but it\u2019s not well understood.
Dr. Ronneberger<\/strong>:<\/strong><\/strong> And it can also change from one time to another. So you might start off with a mild case or slowly progressing, and then it can suddenly become much more severe and quickly progressing. That is the weird thing. And you never know what tomorrow brings.
Dr. Guite: What do you fear the most?<\/strong>
Dr. Ronneberger<\/strong>:<\/strong><\/strong><\/strong>The loss of independence, I\u2019ve already lost a lot of my independence. I mean, I\u2019m 53, and I need help with a lot of things.
And I used to be really independent and extremely active, traveling, doing sports, extremely sociable, you could say, and I loved having people around, and [now] all that is making me really, really fatigued and tired and have to plan everything.
It\u2019s definitely life-changing completely, and I have had to give up my job. I mean, that was my main issue recently. I\u2019ve only given up at the end of January. So I was going to carry on working at least a bit. But unfortunately, that\u2019s not to be now. So that is a big thing.
People are asking: \u201cHow are you getting on with it?\u201d I say: \u201cWell, I feel like something has been amputated.\u201d It\u2019s really like that because I always wanted to be a doctor from when I was about 10.
So there was no other option for me if I hadn\u2019t been a doctor, I would have been a nurse or carer, you know, depending on grades. And I can\u2019t do any of that. Now, I can\u2019t do any paid work now because of my pension. So it\u2019s very hard. So I\u2019m looking for a place to be at the moment.
Dr. Guite: Marianna, what have you found out about the onset of MS through your research in the recent paper in Science<\/em>?<\/strong>
Dr. Cortese: <\/strong>Well, in the recent paper, what stands out is that something that has been a suspicious agent for MS for a long time and investigated by many groups in the world: The Epstein-Barr virus<\/a><\/hl-trusted-source> seems now, with these new findings, to be the leading cause of MS.
This [study] is a collaborative effort that started over 20 years ago with the United States military. The senior authors, my mentors, Dr. Ascherio<\/a> and Dr. Munger<\/a>, really did the mammoth work in this whole project. And it took this long to get together such a big cohort.
[It was] a cohort of U.S. military personnel, comprising 10 million individuals, and they gave 62 million serum samples in total. And in this cohort, we identified those who developed MS during their military service through medical record reviews. There were 955 individuals [in total], and we could access up to three blood samples [for] 800 of these individuals.
We saw that all of them but one person were infected with EBV by the time they developed MS.
And then, we also did an additional analysis looking at who amongst them was negative for EBV at the start of the military duty period, and there were only 35. Then, through [the] follow-up [period], 34 of those seroconverted, meaning they acquired EBV. And then, they went on to develop MS. So only one did not seroconvert.
Among the controls, 107 were EBV-negative at baseline. Only 50% seroconverted, and that corresponds to the actual seroconversion rate. This is how many people acquire EBV in adulthood per year, so this is like the baseline rate.
And in individuals who developed MS, it was almost all that seroconverted, and this leads to the strong risk estimate. This is [why] it seems like acquiring EBV versus remaining negative for EBV leads to a 32 fold increased risk of developing the disease.<\/strong>
This is why we think it is the leading cause of MS because nothing no other risk factor ever looked at comes even close to that. But also, an additional analysis showed increases of a biomarker in the blood, which indicates that there\u2019s already something going on in the brain, that there\u2019s already neural axonal injury going on.
There is another biomarker we measured, and we really see that EBV even precedes increases in this even when the patient doesn\u2019t have symptoms yet, but just a biomarker increase in the blood.
Dr. Guite: I mean, it really is quite extraordinary. This is as strong as the link<\/a><\/hl-trusted-source> between smoking and lung cancer<\/a>. But if you think about the absolute risks of smoking and lung cancer \u2014 if you smoke and carry on smoking through your life, somewhere between one in 20 or 30 people who smoke will get lung cancer, whereas now it\u2019s a different scale if you\u2019re talking about someone with EBV. Can you take us through those absolute risks?<\/strong>
Dr. Cortese:<\/strong> In an adult population, about 95%<\/a> are infected with EBV, were infected at some point in their lives, and remain infected with EBV. Once you get the virus, you remain infected, you cannot clear the body from it.
If we talk about MS, the numbers are one in 200 to 400 individuals developing MS. This is the lifetime risk of one in 200 to 400. It depends on gender, so women are more likely to develop MS. That\u2019s why there\u2019s the range.
So yes, a very common virus is able to cause a relatively rare disease such as MS. And this may seem like a paradox, but it\u2019s actually pretty common in biology that common viruses can lead to rare diseases. So actually MS can be considered a rare complication of an Epstein Barr Virus infection at this point.
And I mean, it\u2019s the same with lung cancer, right? Not everyone who smokes will develop lung cancer, just that the numbers are a little less extreme, but it\u2019s similar here.
Dr. Guite: So Marianna, why has it been so hard to find this association? There\u2019s been a smoking gun around mono<\/a><\/hl-trusted-source> for quite a long time now.<\/strong>
Dr. Cortese:<\/strong><\/strong>The findings from many, many groups over the years have been consistent and really pointing to EBV. However, it was very difficult to talk about causality<\/a>.
To talk about causality, we would need to run a randomized control trial. We would take two groups and expose one group to EBV, the other not and follow them over time, until age 30-40, and see what happens.
Such a study is not possible for obvious reasons. EBV is widespread, you get it from other sources. It\u2019s just not possible to do such a study, and also not ethical.<\/strong>
And so what we tried to do in this study in the military population is find the closest possible study. We wanted to find a group of individuals who were not infected by EBV and follow them over time.
And this is why conducting such a study is so difficult, because EBV is so widespread, so to find individuals that are negative to begin with is difficult. [Moreover,] MS is a relatively rare disease, so to find individuals who were negative in early adulthood and then went on to develop MS is even harder.
This leads to the requirement of such a big number in such a large cohort. And this is why it wasn\u2019t possible to talk about causality so far.
Dr. Guite: Where does this leave other risk factors, such as vitamin D deficiency, smoking, overweight, and exercise as protective?<\/strong>
Dr. Cortese:<\/strong><\/strong><\/strong>There are other factors that have been consistently associated with MS, and what we think is that they remain important since we almost all are infected with EBV.
These factors, such as low vitamin D levels, may further modify the MS risk once you have acquired EBV. So it seems like EBV really makes your risk of developing the disease jump up, but then there are other factors needed that further modify your risk.
Dr. Guite: Marianna, I read that EBV lurks in the B lymphocytes<\/a> forever. So if someone\u2019s got a relapsing remitting type of MS, do you think that\u2019s viral reactivation or something else that\u2019s going on?<\/strong>
Dr. Cortese:<\/strong><\/strong><\/strong><\/strong> That\u2019s definitely one possibility. EBV remains \u2014 we call it \u201clatent\u201d \u2014 in B cells throughout life. It hides in the B lymphocytes from the immune system.
[However,] you shouldn\u2019t imagine every B cell has EBV in it. It\u2019s actually one in 100,000 to 200,000 B cells that you will detect EBV in, but that\u2019s what happens once you acquire EBV. Most people do acquire it in childhood, without any symptoms, and will keep the virus in the B cells.
The virus has evolved to really hide from the immune system, and then intermittently it will reactivate. So the infectious cycles are renewed, and the virus is shed into the saliva, and that\u2019s the transmission route to other people. <\/strong>
And it could remind us of a relapsing remitting disease course, these reactivation cycles. However, we don\u2019t know [for sure], this is definitely one hypothesis. It\u2019s in general not understood and not clear whether EBV is also involved in the disease course.
The study in Science<\/em> does not answer that [question]. This is the next most relevant question: What\u2019s the underlying mechanism with which EBV causes MS? And related to that, depending on the mechanism, [we might infer] whether it is also involved in defining how severe the disease will take its course.
Dr. Guite: After getting to understand the primary cause of a disease, the next step is treatment. So what does this tell us about treatment for MS?<\/strong>
Dr. Cortese: <\/strong>If EBV was also involved in the disease course, as in defining whether someone has more relapses or progresses more rapidly, then you could imagine that targeting the infectious agent more directly could treat the disease in a better way.
And even a cure becomes an option. But there are a lot of \u201cifs;\u201d EBV could also just set up a trigger and then no more play a role once the disease starts. That\u2019s also a possibility. But we need to understand that better.
Dr. Ronneberger<\/strong>:<\/strong><\/strong> Nerve tissue is not able to regenerate easily, is it? So even if you find a cure to get rid of the EBV or vaccination, or an antiviral, even then, you know, the damage is done in a way.
And all nerves are affected \u2014 peripheral, central, everything. So I\u2019m not sure what would be needed to make it regenerate the myelin.
Dr. Cortes<\/strong>e: <\/strong>Earlier treatments could definitely prevent [the myelin damage], but then again how does the early phase of MS, where there are more neural inflammation<\/a> attacks and relapses, affect the longer-term progression?
And how can we prevent the nerve from dying or becoming so vulnerable that it cannot restitute? These are all questions that are somehow related but very relevant, and all the areas are being investigated separately as well.
Dr. Guite: So where does that leave treatments like monoclonal antibodies?<\/strong>
Dr. Cortes<\/strong>e:<\/strong><\/strong> The most potent drugs we have today, the monoclonal antibodies called Ocrelizumab<\/a><\/hl-trusted-source> and Rituximab<\/a><\/hl-trusted-source>, actually target B cells. Think about the B cells as a reservoir of EBV.
More than suppressing the immune system, what it could hint at is that you minimize the B cells that have EBV in them. So this is one argument that maybe EBV plays a role in the disease course. <\/strong>
What these drugs do is minimize the B cells available circulating in the blood. And they\u2019re very effective against at least the neuroinflammatory part of the disease, that is, the relapses. So they\u2019re a little bit like shooting with a cannon, they target B cells in general and can lead to other problems.
So if we were to have more targeted treatments, for example, antivirals, then maybe we could better treat MS, if EBV is involved. So really, the main thing is to find the underlying mechanisms.
Dr. Guite: What are the hopes for the prevention of MS?<\/strong>
Dr. Cortese: <\/strong>The idea of a vaccine is a nice one, and many groups have been working on a vaccine for years. But it is very challenging if we think of MS.
Because you can imagine if people get infected early in life, mainly with EBV, then such a vaccine would need to be given early in life and also convey sterile immunity throughout life.
It\u2019s also difficult to test. If you give a vaccine early in childhood, how are you going to follow people in a trial for 30-40 years? It\u2019s very challenging.
So I think the lower hanging fruit is really the treatment options. [We need] to understand the mechanisms and then, related to what we understand, develop more targeted treatments.
Dr. Ronneberger<\/strong>:<\/strong><\/strong> It\u2019s amazing what you\u2019re doing. And you know, in the last 20 years, I would have never thought that in my life as a doctor, as I\u2019m now at the end of my career, I would see so many different illnesses being treated, like [COVID-19], and now [potentially] MS.
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Millions of people worldwide live with multiple sclerosis (MS), a life-altering, progressive condition. What is the likely cause of MS, and how is medical research advancing towards better treatments? We explore these questions and more in our latest In Conversation podcast.Multiple sclerosis means \u201cmany scars.\u201d It is a chronic condition that mainly affects the central […]<\/p>\n","protected":false},"author":869,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[],"tags":[],"_links":{"self":[{"href":"https:\/\/linksus2.linksus.net\/index.php\/wp-json\/wp\/v2\/posts\/3427"}],"collection":[{"href":"https:\/\/linksus2.linksus.net\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/linksus2.linksus.net\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/linksus2.linksus.net\/index.php\/wp-json\/wp\/v2\/users\/869"}],"replies":[{"embeddable":true,"href":"https:\/\/linksus2.linksus.net\/index.php\/wp-json\/wp\/v2\/comments?post=3427"}],"version-history":[{"count":0,"href":"https:\/\/linksus2.linksus.net\/index.php\/wp-json\/wp\/v2\/posts\/3427\/revisions"}],"wp:attachment":[{"href":"https:\/\/linksus2.linksus.net\/index.php\/wp-json\/wp\/v2\/media?parent=3427"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/linksus2.linksus.net\/index.php\/wp-json\/wp\/v2\/categories?post=3427"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/linksus2.linksus.net\/index.php\/wp-json\/wp\/v2\/tags?post=3427"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}