Harvard study uncovers the cause of multiple sclerosis
[June 9, 2023: Staff Writer, The Brighter Side of News]
Multiple sclerosis (MS), a progressive disease that affects 2.8 million people worldwide and for which there is no definitive cure. (CREDIT: Creative Commons)
A groundbreaking study led by Harvard T.H. Chan School of Public Health researchers has found that the Epstein-Barr virus (EBV) is likely the cause of multiple sclerosis (MS), a progressive disease affecting 2.8 million people worldwide with no definitive cure. The study, published in the journal Science, provides compelling evidence of causality between EBV and MS, and suggests that most cases of MS could be prevented by stopping EBV infection.
“Establishing a causal relationship between the virus and the disease has been difficult because EBV infects approximately 95% of adults, MS is a relatively rare disease, and the onset of MS symptoms begins about 10 years after EBV infection,” said Alberto Ascherio, professor of epidemiology and nutrition at Harvard Chan School and senior author of the study. “This is a big step because it suggests that most MS cases could be prevented by stopping EBV infection, and that targeting EBV could lead to the discovery of a cure for MS.”
MS is a chronic inflammatory disease of the central nervous system that attacks the myelin sheaths protecting neurons in the brain and spinal cord. The cause of MS is unknown, but EBV, a herpes virus that can cause infectious mononucleosis and establishes a lifelong latent infection, is one of the top suspects. The difficulty in establishing a causal relationship is that EBV infects approximately 95% of adults, while MS is a relatively rare disease.
To determine the connection between EBV and MS, the researchers conducted a study among more than 10 million young adults on active duty in the U.S. military and identified 955 who were diagnosed with MS during their period of service.
The team analyzed serum samples taken biennially by the military and determined the soldiers’ EBV status at the time of the first sample and the relationship between EBV infection and MS onset during the period of active duty.
In this cohort, the risk of MS increased 32-fold after infection with EBV but was unchanged after infection with other viruses. Serum levels of neurofilament light chain, a biomarker of the nerve degeneration typical in MS, increased only after EBV infection. The findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.
Ascherio says that the delay between EBV infection and the onset of MS may be partially due to the disease’s symptoms being undetected during the earliest stages and partially due to the evolving relationship between EBV and the host’s immune system, which is repeatedly stimulated whenever latent virus reactivates.
Study results table: Residual serum samples from the DoDSR were obtained from 810 MS patients and 1577 matched controls. We assessed whether individuals were seropositive for EBV and CMV in up to three serum samples per person. We measured sNfL in those who were EBV-negative in the first serum sample. VirScan was used to profile the virome in a subset of MS cases with serum samples collected shortly before and after symptom onset. (CREDIT: Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis study)
“Currently there is no way to effectively prevent or treat EBV infection, but an EBV vaccine or targeting the virus with EBV-specific antiviral drugs could ultimately prevent or cure MS,” said Ascherio.
MS is a debilitating disease that can lead to blindness, paralysis, and cognitive impairment. The study’s findings offer new hope for prevention and treatment of MS.
Serum levels of neurofilament light chain, a biomarker of the nerve degeneration typical in MS, increased only after EBV infection. (CREDIT: Harvard University)
The EBV virus was discovered in 1964 and is one of the most common viruses worldwide. It is estimated that over 90% of adults have been infected with EBV, with the majority of infections occurring during childhood. EBV is the cause of infectious mononucleosis, or “mono,” a viral illness that causes fever, sore throat, and fatigue, and is most common in adolescents and young adults.
EBV has also been linked to other diseases, such as some types of cancer, including Hodgkin lymphoma, Burkitt lymphoma, and nasopharyngeal carcinoma. The study’s authors note that if EBV is confirmed as the cause of MS, it could have important implications for the prevention and treatment of other diseases associated with the virus.
The Harvard T.H. Chan School of Public Health researchers are not the first to suggest a link between EBV and MS. Earlier studies have found that people with MS tend to have higher levels of antibodies to the virus compared to those without the disease. However, this new study is the first to provide compelling evidence of causality between the virus and MS.
The study’s findings have generated excitement among the scientific community, with many experts calling the research a “game changer” in the field of MS research. Dr. Timothy Coetzee, chief advocacy, services, and research officer at the National Multiple Sclerosis Society, called the study “a significant advance in our understanding of the biology of MS.”
Coetzee added that the findings “underscore the importance of continued investment in research to identify the cause or causes of MS, and to develop effective therapies that can halt or reverse the damage caused by the disease.”
While there is currently no cure for MS, there are a number of treatments available that can help manage the symptoms and slow the progression of the disease. However, these treatments are not effective for all patients and can have serious side effects.
If EBV is indeed the cause of MS, this could lead to the development of more effective treatments and potentially a cure for the disease. Researchers may be able to develop an EBV vaccine or EBV-specific antiviral drugs that could prevent or cure MS.
The study’s authors caution that more research is needed to confirm the link between EBV and MS and to determine how the virus triggers the disease. However, they are optimistic about the potential of their findings.
“We are excited about the possibility that our findings could lead to a cure for MS,” said Ascherio. “This study provides strong evidence that targeting EBV is a promising strategy for preventing and treating MS and other diseases associated with the virus.”
The next step for researchers will be to conduct further studies to better understand the relationship between EBV and MS, and to develop new treatments based on these findings. While a cure for MS may still be years away, the discovery of the link between the virus and the disease represents a major breakthrough in the fight against this debilitating condition.
Recent developments or emerging therapies for Multiple Sclerosis
Bruton's tyrosine kinase (BTK) inhibitor is an emerging therapy being studied in relapsing-remitting MS and secondary-progressive MS. It works by predominantly modulating B cells and microglia which are immune cells in the central nervous system.
Stem cell transplantation is a therapy that destroys the immune system of someone with MS and then replaces it with transplanted healthy stem cells. Researchers are still investigating whether this therapy can decrease inflammation in people with MS and help to "reset" the immune system. Possible side effects are fever and infections.
Researchers are learning more about how existing DMTs work to lessen relapses and reduce MS-related lesions in the brain. Further studies will determine whether treatment can delay disability caused by the disease.
Symptoms of Multiple Sclerosis
According to the Mayo Clinic, multiple sclerosis signs and symptoms may differ greatly from person to person and over the course of the disease depending on the location of affected nerve fibers. Symptoms often affect movement, such as:
Numbness or weakness in one or more limbs that typically occurs on one side of your body at a time, or your legs and trunk
Electric-shock sensations that occur with certain neck movements, especially bending the neck forward (Lhermitte sign)
Tremor, lack of coordination or unsteady gait
Vision problems are also common, including:
Partial or complete loss of vision, usually in one eye at a time, often with pain during eye movement
Prolonged double vision
Multiple sclerosis symptoms may also include:
Tingling or pain in parts of your body
Problems with sexual, bowel and bladder function
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