For decades, researchers have suspected that people infected with an extremely common virus, Epstein-Barr, might be more likely to develop multiple sclerosis, a neurological disease that affects one million people in the United States. Now a team of researchers is reporting what some say is the most compelling evidence yet of a strong link between the two diseases.
The virus infects almost everyone in adolescence or early adulthood, and very few develop multiple sclerosis. The researchers also note that this is not the only known risk factor for people who develop the disease. But they say their data indicates it is the clearest of all. While it remains to be seen whether the discovery will translate into treatments or cures for multiple sclerosis, the study could further motivate the search for therapies and vaccines for the disease.
In their study, published Thursday in Science, the group looked at data from 10 million people on active duty in the US armed forces over two decades. The strength of their study, said its lead researcher, Dr. Alberto Ascherio, an epidemiologist at Harvard TH Chan School of Public Health, is that they were able to follow people for years and ask whether Epstein-Barr infections have preceded multiple sclerosis.
Among the soldiers participating in the study, 801 developed multiple sclerosis, a disabling disease that occurs when the immune system attacks the fatty insulation that protects nerves in the brain and spinal cord. Most people who develop the disease are diagnosed between the ages of 20 and 50. However, the disease is rare – the risk of an individual contracting multiple sclerosis is 0.5%.
At the same time, the virus in question, Epstein-Barr, is common, infecting nearly everyone in the population at some point. Although few are aware that they have been infected, some develop mononucleosis. The virus remains in the body for life.
Since so few people infected with the virus get multiple sclerosis, it cannot be the sole cause of the disease. Other risk factors were identified, including some, such as low vitamin D levels and smoking, that were previously observed by the Harvard group using the same data set. There are also genetic factors – 900 abnormal genes have been identified in patients with multiple sclerosis, said Dr Anthony J. Reder, an expert in multiple sclerosis at the University of Chicago, who was not involved in the the new study. Gender also plays a role; most patients are women.
But, Dr. Ascherio said, no single risk factor stands out like Epstein-Barr infections.
To ask how much the virus increases risk, investigators studied the small proportion of people who were not infected with the virus early in their military careers but later became infected. They detected infections by the presence of antibodies against the virus.
Among multiple sclerosis patients, 32 out of 33 were infected with Epstein-Barr before developing MS
As a control group for their study, the scientists followed 90 people who were not initially infected with Epstein-Barr and who also did not contract multiple sclerosis. Of these, only 51 were subsequently infected with Epstein-Barr.
This meant that infection with the Epstein-Barr virus increased the risk of multiple sclerosis more than 30 times, Dr Ascherio said.
But Dr Reder warned it could be difficult to disentangle cause and effect from an epidemiological study. People who develop multiple sclerosis have an overactive immune system that causes them to develop high levels of antibodies against viral infections. Multiple sclerosis can occur not because of the virus, but because of the body’s response to it.
“Patients with multiple sclerosis have fewer viral infections than normal,” he said, because their immune systems are so active that they effectively fight off viruses. “Patients with multiple sclerosis often say, ‘I never catch a cold.’ When I hear that, my ears perk up.
Drugs currently used to treat multiple sclerosis weaken the immune system, Dr. Reder noted. So far, he added, antiviral drugs have not helped patients with multiple sclerosis.
The Harvard group tried to control for the possibility that the immune system response, not the virus itself, increases the risk of multiple sclerosis in people infected with Epstein-Barr. They asked whether antibodies to another common virus, cytomegalovirus, were also linked to an increased risk of multiple sclerosis. They were not.
But cytomegalovirus, Dr. Reder said, for unknown reasons, appears to protect against multiple sclerosis. Thus, the fact that infected people do not have a higher risk of multiple sclerosis is perhaps not surprising.
Others said the study was compelling evidence of cause and effect.
“The way it was done is pretty compelling,” said Johns Hopkins multiple sclerosis specialist Dr. Michael David Kornberg. “This is really the most compelling data we’ve had for a causal association.”
This leaves the question of what to do now.
Dr Bruce Cree, a multiple sclerosis researcher at the University of California, San Francisco, noted that it could be difficult to treat multiple sclerosis by tackling Epstein-Barr because it can be difficult to find the actual virus in patients. Even though multiple sclerosis is a disease of the brain and spinal cord, he could not find the virus in the patients’ cerebrospinal fluid.
But patients seem to harbor cells in their brains that produce antibodies against the Epstein-Barr virus. Dr. Cree is investigating whether he can treat patients with multiple sclerosis by eradicating Epstein-Barr infected cells.
And Stanford multiple sclerosis researcher Dr Lawrence Steinman, who wrote an outlook accompanying the Harvard group’s paper, said an experimental mRNA vaccine against Epstein-Barr was one of several approaches designed. to prevent the virus from affecting the brain.
The question now, he said, is, “Can we make multiple sclerosis go away?”