New Research Links Epstein-Barr Virus to Multiple Sclerosis

IRA FLATOW: This is Science Friday, I’m Ira Flatow. A group of scientists at Harvard say they have made a major breakthrough in understanding multiple sclerosis. For years they have been testing out a hypothesis that the Epstein Barr Virus causes MS. Yes, that’s the same virus responsible for mononucleosis. Researchers analyzed the database of 10 million active duty military members. And they found that service members who contracted the Epstein Barr Virus were 32 times more likely to be diagnosed with MS. The research was published in the journal Science. To help us better understand this research and its impact is the study’s senior author, Dr. Alberto Ascherio. He’s a professor of epidemiology and nutrition at the Harvard T.H. Chan School of Public Health. Welcome to Science Friday.

ALBERTO ASCHERIO: Thank you.

IRA FLATOW: Tell me about what you found. How were you able to determine that people who had previously contracted the Epstein Barr Virus were much more likely to be diagnosed with MS.

ALBERTO ASCHERIO: Right. We started with people who were not infected with the EBV virus. So we followed them over time for an average of 10 years. And basically, we found that those individual were not infected with EBV, they never develop MS. So only after they got infected with EBV, then the risk of MS jumped out over 30 fold.

IRA FLATOW: Well, 10 million people, that’s a pretty big sample, is it not?

ALBERTO ASCHERIO: Yeah, it was necesssary because EBV infects virtually everyone, so it’s not easy to find a large population of individuals who are not infected with EBV. So [inaudible] medium only roughly 5% were EBV negative at the beginning of this study.

IRA FLATOW: Tell us how this has changed how we understand MS as a disease.

ALBERTO ASCHERIO: Well, MS has been that typically described even today as an autoimmune disease of unknown etiology, meaning we don’t know the cause of it. So I think that should change to say we now know that MS is a rare complication and I want to emphasize rare complication of EBV infection. I don’t want any listener to be scared though I had mononucleosis I’m going to get MS. The risk is still very small.

IRA FLATOW: Okay, so you say it’s very rare. Why do you think that EBV might be causing MS? What is the what is the cause?

ALBERTO ASCHERIO: You know, we are quite confident that EBV is the cause. So it’s a common setting for a virus to be relatively harmless in the majority of people but cause a severe disease as a complication. A good example is polio myelitis. Before we had the vaccine, the polio virus would infect virtually every child in the country, but only 1 in 400 children would get paralytic disease.

IRA FLATOW: Now, MS is an autoimmune disease, correct? The body attacks itself. What is the mechanism, you might think, that EBV causes this to happen?

ALBERTO ASCHERIO: Immunity in autoimmune plays an important role as a mechanism. But I don’t think the definition autoimmune disease give the full story. So this is a complication of a viral infection in which the immune system plays an important role in, you know, in in the pathology.

IRA FLATOW: Now, I understand that you’ve had a hunch for a while that Epstein-Barr was one of the main drivers of MS. Were you surprised, though, by the strength of this relationship between EBV and MS?

ALBERTO ASCHERIO: I was surprised by how clear cut the results were. You know, I did expect a strong association. But I didn’t expect to be so black and white. Because almost never in science, you see a result that are so so neat. So, we look not only at testing [Epstein-]Barr virus. We also had several controls in our study. One is the CMV virus, which is a virus transmitted in a similar manner to EBV. And what we found that that there is absolutely no association between CMV infection and MS. Now in addition, we did a screening of all the human virome, so we look at antibody responses against all the known human viruses. And all the signal that came out were a signal from EBV peptides, so we were still astonished to see there was no noise, no false signal coming from anywhere else. EBV is so strong that overwhelms everything else.

IRA FLATOW: Now do we know why some people you talked about how rare it is to get EBV and then develop MS. Do we know why some people do develop MS from EBV?

ALBERTO ASCHERIO: We know that there are some factors that were also infected with EBV. Your risk may be related to your genetic susceptibility that can increase the risk by two, three-fold. We previously discovered that vitamin D deficiency is a risk factor for MS. It can double your risk. Cigarette smoking can double your risk of MS and childhood obesity may cause an increase of 40-50%. So these factors together modulate the risk but EBV stand out with a different magnitude.

IRA FLATOW: Have you found a cause and effect yet? Or is this basically just a relationship that you’ve discovered?

ALBERTO ASCHERIO: I believe it’s the cause and effect. And you know, some people will question that, but it’s, you know, even the link between smoking and lung cancer has been questioned. So, there is no experimental evidence directly that you randomize people to smoke or not smoke and get or not get lung cancer. We are in the same realm of evidence. This is a longitudinal study, rigorously controlled in the large population. And there is not really alternative plausible explanation. Now, when we say “cause” in epidemiology, we mean if we could prevent the infection, we are going to prevent MS. You prevent A, B will not happen. It doesn’t mean we fully understand all the molecular mechanisms.

IRA FLATOW: That leads me to my next question, which is, how might this discovery help find better treatments or even a cure for MS?

ALBERTO ASCHERIO: Well, the current treatment of MS are the most effective drugs are called anti-CD20 antibodies or Ocrelizumab. Ocre was the commercial name. So the effect of this drug is to deplete the B cells. The B cells are part of our immune system, in that the primary site of persistence of the EBV virus in our body. So EBV, once it infect one person, will remain in the B cell for the rest of this person’s life. So I think anti-CD20 are so effective because they deplete the B cell, and by depleting the B cells, they also take away the virus. So it makes sense to target the virus directly with antiviral drug instead of depleting the B cells which are important after the immune system.

IRA FLATOW: Could you target the virus as a vaccine to prevent infection? Or could you target it also after the MS has occurred?

ALBERTO ASCHERIO: Oh, both are possible. There is ongoing research and a vaccine. Moderna is a vaccine in phase 1 experimentation against the EBV. Now a vaccine to prevent MS would have to prevent EBV infection. If the vaccine does not fully prevent infection, it’s difficult to predict what the effect of MS or MS could be.

IRA FLATOW: Is this Moderna clinical trial, using an mRNA technology you’re talking about, is it very exciting for you?

ALBERTO ASCHERIO: It is. It’s a very early phase, so, it will take a few years before a vaccine is ready for large scale experimentation. And also because the infection typically occurs in childhood, to see where it prevent the best will take several years more. So we have to be patient. It’s the long term project.

IRA FLATOW: And so where do you go from here? What’s your next step?

ALBERTO ASCHERIO: Well, we we are, as I mentioned, we are collaborating with clinical groups trying to test antiviral drugs in people with MS. We’re trying to get funding for that. I think that the most exciting, the most exciting part. In terms of the epidemiology, I think would be also very useful if you could predict among these people who are a being infected, who is going to get MS, who is not going to get MS. So more work on biomarkers is also a another line of investigation that we are pursuing.

IRA FLATOW: You know, anytime somebody calls something a breakthrough in medicine, other people say, wait just a minute, that’s a big term to use breakthrough. Do you consider this a real breakthrough?

ALBERTO ASCHERIO: I do. But it’s not easy to change people’s mind. You know, once you’ve been thinking on a disease in a certain way for 20-30 years and for your entire career, it’s not easy to change the mindset and accept that we have a new paradigm.

IRA FLATOW: What are your, what are your colleagues saying about this? Are they excited about this? Or are they still saying hey, you know, we see… need to see some more evidence.

ALBERTO ASCHERIO: This is, you know, it’s a very, very widespread go from people who are very excited and entirely agree with us, you know, then you have the people who deny the evidence and everything in between. I think, you know, it’s very, very diverse.

IRA FLATOW: What do you attribute your success to? Is it just dogged determination that you are going to find something here and go through all those viruses and come up with some cure?

ALBERTO ASCHERIO: No. With the the right intuition, the right hypothesis in the beginning was, was key to this. The identification of the right population, the patience in establishing, you know, long series of complex collaboration with multiple institutions, and having an amazing team of collaborators here, and then within the military that made this possible. It was 20 years of work to, to complete this research.

IRA FLATOW: There are going to be people who have MS who, who were going to say, hey, there’s a cure around the corner.

ALBERTO ASCHERIO: Right. For people who have MS, I think, yeah, I would be excited on one hand, but also understand that the time frame for this things is measuring in years. So short term, would be five years. Let me say this, you know my over optimistic view to translate this into a new treatment, I would give myself five years of time in the best possible scenario.

IRA FLATOW: And finally, does this have implications for how we understand diseases perhaps or the mechanisms perhaps for Alzheimer’s or chronic fatigue syndrome? Where you know, a virus may be involved, and we just don’t know that yet.

ALBERTO ASCHERIO: Right. Well, it showed that yes, is in some way that it showed that we don’t really and fully understand the viruses and the effect that they have in the long term. So we are particularly interested in a disease like Alzheimer’s, there is a lot of interest in a potential effect of infection, a potential contribution of infection for sign of disease and that is an area that our group is initiating to explore. In also in relation with ALS, amyotrophic lateral sclerosis, but we have not, we are very much behind compared to… I hope it will take less than 20 years, but it will take time before we can elucidate those associations.

IRA FLATOW: Well, Dr. Ascherio, congratulations to you on the publication of your paper and we wish you good luck.

ALBERTO ASCHERIO: Thank you very much. Huge pleasure and an honor to be talking with you.

IRA FLATOW: Dr. Alberto Ascherio, professor of epidemiology and nutrition at the Harvard T.H. Chan School of Public Health. This is Science Friday from WNYC Studios.