Soon a vaccine against multiple sclerosis? This is the encouraging prospect envisaged by a recent study which demonstrates for the first time that the Epstein-Barr virus is the main cause of this autoimmune disease which damages the central nervous system. The article, published on January 13, 2021 in the journal Science, is therefore a source of hope for the 2.8 million people who suffer from this disease, for which there is as yet no vaccine or cure. Science and Future asked Harvard University epidemiologist Alberto Ascherio, director of the study, who explains to us why it was so difficult to prove this causal link as well as the therapeutic avenues envisaged.
Sciences et Avenir: What did we know about the link between the Epstein-Barr virus and multiple sclerosis before this study?
Alberto Ascherio: This link has been suspected for more than 40 years, but the prevailing thought was that this association did not imply causation. Most of the medical literature defines multiple sclerosis as an autoimmune disease with an unknown cause. Because it was very difficult to establish this causal link: the Epstein-Barr virus is present in the vast majority of people (it is estimated that this is the case for around 95% of the world’s population), so all people with multiple sclerosis had the virus, but also the majority of people without the disease. It’s as if we were in a country where everyone smokes, some will develop lung cancer, but it’s very complicated to demonstrate that it’s because of cigarettes, because the majority of those who smoke don’t will not have this cancer.
And then, how did you demonstrate this causal link?
This is the first time that we have followed a large cohort of young women and men for so long (nearly 10 years), many of whom did not have the virus at the start of the study.
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Soon a vaccine against multiple sclerosis? This is the encouraging prospect envisaged by a recent study which demonstrates for the first time that the Epstein-Barr virus is the main cause of this autoimmune disease which damages the central nervous system. The article, published on January 13, 2021 in the journal Science, is therefore a source of hope for the 2.8 million people who suffer from this disease, for which there is as yet no vaccine or cure. Science and Future asked Harvard University epidemiologist Alberto Ascherio, director of the study, who explains to us why it was so difficult to prove this causal link as well as the therapeutic avenues envisaged.
Sciences et Avenir: What did we know about the link between the Epstein-Barr virus and multiple sclerosis before this study?
Alberto Ascherio: This link has been suspected for more than 40 years, but the prevailing thought was that this association did not imply causation. Most of the medical literature defines multiple sclerosis as an autoimmune disease with an unknown cause. Because it was very difficult to establish this causal link: the Epstein-Barr virus is present in the vast majority of people (it is estimated that this is the case for around 95% of the world’s population), so all people with multiple sclerosis had the virus, but also the majority of people without the disease. It’s as if we were in a country where everyone smokes, some will develop lung cancer, but it’s very complicated to demonstrate that it’s because of cigarettes, because the majority of those who smoke don’t will not have this cancer.
And then, how did you demonstrate this causal link?
This is the first time that we have followed a large cohort of young women and men for so long (nearly 10 years), many of whom did not have the virus at the start of the study. Those who were not infected during this period did not develop the disease, while almost all those who did had the virus. Thus, the infection multiplied by 30 the risk of having multiple sclerosis. We have also shown that the infection precedes the onset of multiple sclerosis as well as any precursor signal of this disease, such as the accumulation of neurofilaments which is a biomarker of a neurodegenerative disease. So it’s very clear now that infection is the first event, followed by an asymptomatic increase in this marker, and ultimately the onset of disease, a process that takes months or even years. And we also show that this link does not exist with other viruses, it is specific to the Epstein-Barr virus.
What is the mechanism by which the virus causes multiple sclerosis?
It is likely that the immune response against the Epstein-Barr virus is misdirected and attacks brain cells. So it’s not the virus directly that causes the disease, but the immune system that tries to eliminate the virus, but ends up damaging the brain.
However, most people infected with the Epstein-Barr virus do not develop multiple sclerosis. Why ?
It is indeed very important to reassure the general public: even if you catch the virus, you will not necessarily have multiple sclerosis. It’s like the poliovirus, responsible for poliomyelitis: before vaccination against this virus, all children caught it, but only 1 in 400 developed the characteristic paralysis of polio, and we have never understood why. Similarly for cigarettes and lung cancer, smoking multiplies the risk by 20, but the majority of smokers do not develop this cancer. Because there are other factors at play and it is difficult to identify them. For multiple sclerosis, we know certain risk factors, such as a low level of vitamin D, tobacco, childhood obesity or genetic predisposition that double the risk. But the most determining factor is infection with the Epstein-Barr virus, which increases the risk 10 times more than these other factors.
Now that we know the Epstein-Barr virus is the leading cause of multiple sclerosis, what can we do?
Currently, the basic treatment is to attack the B cells of the immune system, because it is in these cells that the Epstein-Barr virus mainly hides. So by reducing the number of these lymphocytes, we also attack the virus. But we need B cells to produce antibodies against other pathogens so this treatment may make patients more vulnerable. It would thus be much better to target the virus directly without touching the lymphocytes.
We could, for example, develop a vaccine against the virus that would prevent infection and thus prevent the vast majority of cases of multiple sclerosis. Moderna is already working on an RNA vaccine against this virus, as well as the American Institutes of Health (NIH). We can also design an antiviral to treat people with the disease, because it is likely that by eliminating the virus we could improve the treatment of multiple sclerosis and perhaps even cure this disease. Our lab is currently collaborating with others to design a clinical trial of several antivirals that may be effective against the Epstein-Barr virus.
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