How Can a Common Virus Cause Multiple Sclerosis? New Study Explains

Epstein Barr Virus - The Epstein-Barr Virus (EBV), a type of herpesvirus, is one of the most commonly found viruses in humans. It’s estimated that over 90% of people globally are carriers of EBV, maintaining a latent and typically symptom-free infection throughout their lives. The majority of individuals are infected during childhood and exhibit little to no symptoms. However, in young adults, EBV often leads to infectious mononucleosis, colloquially known as glandular fever or the kissing disease.

Scientists from the Karolinska Institute in Sweden have uncovered further evidence regarding the Epstein-Barr virus’s role in initiating or escalating multiple sclerosis. The study, published in Science Advances, indicates that certain individuals possess antibodies against this virus that inadvertently target a protein located in the brain and spinal cord.

The Epstein-Barr virus (EBV) typically infects individuals during early life, remaining within the body indefinitely without triggering noticeable symptoms. The link between EBV and the neurological disease multiple sclerosis (MS) was discovered many years ago and has puzzled researchers ever since.

Increasing evidence, including two papers published in Science and Nature last year, suggests that EBV infection precedes MS and that antibodies against the virus may be involved. However, the molecular mechanisms seem to vary between patients and remain largely unknown.

“MS is an incredibly complex disease, but our study provides an important piece in the puzzle and could explain why some people develop the disease,” says Olivia Thomas, a postdoctoral researcher at the Department of Clinical Neuroscience, Karolinska Institutet and shared first author of the paper. “We have discovered that certain antibodies against the Epstein-Barr virus, which would normally fight the infection, can mistakenly target the brain and spinal cord and cause damage.”

Misdirected antibodies The researchers analyzed blood samples from more than 700 patients with MS and 700 healthy individuals. They found that antibodies that bind to a certain protein in the Epstein-Barr virus, EBNA1, can also bind to a similar protein in the brain and spinal cord called CRYAB, whose role is to prevent protein aggregation during conditions of cellular stress such as inflammation. These misdirected, cross-reactive antibodies may damage the nervous system and cause severe symptoms in MS patients, including problems with balance, mobility, and fatigue. The antibodies were present in about 23 percent of MS patients and 7 percent of control individuals.

“This shows that, whilst these antibody responses are not required for disease development, they may be involved in disease in up to a quarter of MS patients,” says Olivia Thomas. “This also demonstrates the high variation between patients, highlighting the need for personalized therapies. Current therapies are effective at reducing relapses in MS but unfortunately, none can prevent disease progression.”

T cells may also be involved The researchers also found that there is likely a similar cross-reactivity among T cells of the immune system.

“We are now expanding our research to investigate how T cells fight EBV infection and how these immune cells may damage the nervous system in multiple sclerosis and contribute to disease progression,” says Mattias Bronge, affiliated researcher at the Department of Clinical Neuroscience, Karolinska Institutet and shared first author of the paper.

Reference: “Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis” by Olivia G. Thomas, Mattias Bronge, Katarina Tengvall, Birce Akpinar, Ola B. Nilsson, Erik Holmgren, Tara Hessa, Guro Gafvelin, Mohsen Khademi, Lars Alfredsson, Roland Martin, André Ortlieb Guerreiro-Cacais, Hans Grönlund, Tomas Olsson and Ingrid Kockum, 17 May 2023, Science Advances. DOI: 10.1126/sciadv.adg3032

The study was financed by Sweden’s innovation agency Vinnova, the Swedish Research Council, the Swedish Brain Foundation, Karolinska Institutet, MS Forskningsfonden, Neuro, and Region Stockholm. Co-author Hans Grönlund is the inventor of a current patent filed by NEOGAP Therapeutics AB and is the founder and co-owner of this company. Birce Akpinar, Ola B. Nilsson, Erik Holmgren and Guro Gafvelin hold positions at NEOGAP Therapeutics AB. Roland Martin is a co-founder, co-owner and an employee of Cellerys, a spin-out from the University of Zürich, and is a coinventor and patent holder for several patents. Roland Martin and Tomas Olsson have received grants and fees from several companies. See the scientific paper for a complete list of the authors’ potential conflicts of interest.

Amazing progress has been made against MS in the last 25 years.

The death toll has dropped to near zero for younger people, and severe disability has been significantly reduced.

A female cousin in my family, who was in perfect health, was stricken in the 1980s. It killed her in five years, before her 40th birthday.

Remarkably, she lived near the Mayo Clinic in Minnesota, which was the world leader in MS treatment at that time. She had the best medical care in the world, but, still dead in five years.

One other curious fact about MS - the further north you live, the higher the risk you have for MS.

The cure exists - fecal transplants

Fecal Microbiota Transplantation in Multiple Sclerosis

Borody, Thomas MD, PhD, FACG; Leis, Sharyn BN; Campbell, Jordana BSc; Torres, Margaux BSc; Nowak, Anna BMedSc
American Journal of Gastroenterology: October 2011 - Volume 106 - Issue - p S352

Purpose: Recent evidence implicates the GI microbiota in the progression of neurological diseases such as Parkinsons Disease1, Multiple Sclerosis and Myasthenia Gravis2. We report three patients with MS diagnoses who achieved durable symptom reversal with FMT for constipation.

Methods: Case study observations on three MS cases

Results:
Case 1: A 30 yr old male with constipation, vertigo and impaired concentration and a concomitant history of MS and trigeminal neuralgia. Neurological symptoms included severe leg weakness and he required a wheelchair and an indwelling urinary catheter. Previous failed treatments included Mexiletine, Tryptanol and β-interferon. The patient underwent 5 FMT infusions for his constipation, with its complete resolution. Interestingly his MS also progressively improved, regaining the ability to walk and facilitating the removal of his catheter. Initially seen as a ‘remission', the patient remains well 15 yrs post-FMT without relapse.

Case 2: A 29 yr old wheelchair-bound male with ‘atypical MS' diagnosis and severe, chronic constipation. He reported parasthesia and leg muscle weakness. The patient received 10 days of FMT infusions which resolved his constipation. He also noted progressive improvement in neurological symptoms, regaining the ability to walk following slow resolution of leg parasthesia. Three years on the patient maintains normal motor, urinary and GI function.

Case 3: An 80 yr old female presented with severe chronic constipation, proctalgia fugax and severe muscular weakness resulting in difficulty walking, diagnosed as ‘atypical' MS. She received 5 FMT infusions with rapid improvement of constipation and increased energy levels. At eight months she reported complete resolution of bowel symptoms and neurological improvement, now walking long distances unassisted. Two years post-FMT, the patient was asymptomatic.

Conclusion: We report reversal of major neurological symptoms in three patients after FMT for their underlying GI symptoms. As MS can follow a relapsing-remitting course, this unexpected discovery was not reported until considerable time had passed to confirm prolonged remission. It is tempting to speculate that FMT achieved eradication of an occult GI pathogen driving MS symptoms. Our finding that FMT can reverse MS-like symptoms suggests a GI infection underpinning these disorders. It is hoped that such serendipitous findings may encourage a new direction in neurological research.

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