Groundbreaking research identifies the cause of multiple sclerosis

[Nov. 9, 2022: Nicole Rura, Harvard T.H. Chan School of Public Health]


Multiple sclerosis (MS), a progressive disease that affects 2.8 million people worldwide and for which there is no definitive cure. (CREDIT: Creative Commons)


Multiple sclerosis (MS), a progressive disease that affects 2.8 million people worldwide and for which there is no definitive cure, is likely caused by infection with the Epstein-Barr virus (EBV), according to a study led by Harvard T.H. Chan School of Public Health researchers.


“The hypothesis that EBV causes MS has been investigated by our group and others for several years, but this is the first study providing compelling evidence of causality,” 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. Its cause is not known, yet one of the top suspects is EBV, a herpes virus that can cause infectious mononucleosis and establishes a latent, lifelong infection of the host.


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 ten years after EBV infection.


 

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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 time of 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.


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)


 
 

Ascherio says that the delay between EBV infection and the onset of MS may be partially due 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.


Serum levels of neurofilament light chain, a biomarker of the nerve degeneration typical in MS, increased only after EBV infection. (CREDIT: Harvard University)


“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.


 
 

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.





For more science and technology stories check out our New Discoveries section at The Brighter Side of News.


 

Note: Materials provided above by Harvard T.H. Chan School of Public Health. Content may be edited for style and length.


 
 

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