Multiple Sclerosis

Multiple Sclerosis is Likely Caused by a Virus, Says Study

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US military study suggests that the Epstein-Barr virus may be a leading cause of Multiple Sclerosis (MS). Image courtesy of HealthCentral.

Multiple Sclerosis (MS), a debilitating autoimmune disease, may in fact be caused by a virus, suggests a new study published in Science by Harvard Medical School Researchers.

The researchers tested a cohort of more than 10 million young adults on active duty in the US military between 1993 and 2013. During this 20-year timeframe, 955 individuals were diagnosed with MS over the course of their period of service. The researchers found that the risk of MS increased 32-fold after infection with the Epstein-Barr virus, known as EBV for short.

MS is a chronic inflammatory demyelinating disease of the central nervous system. The chronic inflammation occurs when the immune system mistakenly attacks the protective sheath (myelin) that covers nerve fibers, causing communication problems between your brain and the rest of your body. According to the Mayo Clinic, the disease can eventually cause permanent damage or deterioration of the nerves. Other symptoms include vision problems, slurred speech, fatigue, dizziness, tingling or pain in parts of the body, and bowel, bladder, and sexual dysfunction.

Multiple Sclerosis and the Epstein-Barr Virus

Although the exact cause of multiple sclerosis is unknown, it has long been hypothesized that the demyelination in the brain and spinal course is triggered by a viral infection. This particular study found that serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion, suggesting that EBV is a leading cause of MS. However, the risk of MS was not increased after infection with other viruses, such as the cytomegalovirus (CMV); the researchers had also compared samples to CMV positivity as a negative control group, and found that CMV positivity was actually associated with a lower risk of MS.

“The key finding is that MS is a complication of infection with EBV,” said Alberto Ascherio, a professor of epidemiology and nutrition at Harvard’s T.H. Chan School of Public Health. Commenting on the size and longevity of the study, Ascherio said: “There is no comparable population in the world.”

Stanford University researchers believe that molecular mimicry may be the culprit behind why those infected with Epstein-Barr have a higher risk of developing MS. Molecular mimicry occurs when immune cells targeting EBV accidentally attack myelin, due to the molecular similarities between the virus and this tissue. A 2018 study identified EBV-infected B cells in the brains of MS patients, lending support to the molecular mimicry theory.

Deficiency of vitamin D from the sun may also play a role in the development of MS. Image courtesy of Minnesota Oncology.

Multiple Sclerosis: Vitamin D Deficiency and Genetic Factors

It’s unlikely that EBV is the sole reason behind the development of MS, however. The study suggests that EBV seropositivity is necessary to develop MS, but it isn’t sufficient – otherwise, 95% of the world’s population would have MS, since the virus is prevalent worldwide. According to the UK-based Multiple Sclerosis Trust, an estimated 2.5 million people worldwide have multiple sclerosis. So why do only some people develop MS and not others?

Another theory about the development of MS is vitamin D deficiency. Vitamin D, also known as the sunshine vitamin, may be a protective compound against the development of MS; it has been found, for instance, that the distribution of MS around the world is uneven; generally, the prevalence of the disease increases as you travel further north or south from the equator. The parts of Asia, Africa and America that lie on the equator have extremely low levels of MS, while Canada and Scotland have particularly high rates. This suggests that vitamin D, particularly from the sun, is important in preventing MS, possibly due to its anti-inflammatory properties.

Other studies have shown that certain ethnic groups have a markedly lower prevalence of MS, despite living in places where the disease is more common. For example, the Sami or Lapps of northern Scandinavia, the Inuits of Canada and Greenland (Denmark), and the Maoris of New Zealand exhibit very low rates of MS, despite living in some of the northernmost and southernmost climates in the world.

The Inuit people of Canada and Greenland have very low rates of MS among their population, despite living in some of the northernmost regions of the world. Photo courtesy of The Paleo Diet.

Multiple Sclerosis and Diet

Another theory that has evolved is the relationship between Multiple Sclerosis and one’s diet. As noted above, many northernmost communities do not get sufficient vitamin D from the sun, due to their local climate. However, they make up for this by consuming a vitamin D-rich diet; for example, fish and marine mammals like seal and whale. These foods are also rich in healthy omega-3 fatty acids, which are also known to have anti-inflammatory properties and may help other autoimmune conditions beyond MS, like rheumatoid arthritis, Crohn’s disease, ulcerative colitis, and systemic lupus erythematosus.

Although considered controversial to some, Dr. Terry Wahls, who has multiple sclerosis herself, developed a dietary approach to treating autoimmune conditions with paleo principals, which she calls the Wahls Protocol.

New Ways to Treat MS

Ascherio, for his part, believes that his team’s groundbreaking research on the connection between viruses like Epstein-Barr and MS could pioneer the development of new multiple sclerosis treatments. For example, immunosuppressive therapies that deplete B cells infected by EBV.

There is also renewed interest in developing vaccines and antivirals against EBV with the objective of eradicating MS. While antivirals targeting EBV don’t yet exist, Ascherio says their development is realistic: “Once you establish the causal connection, I think it’s a question of providing sufficient rational for research on antivirals, specifically for EBV, that could help people with MS [around] the world,” he concluded.

Christina Applegate Reveals Multiple Sclerosis Diagnosis

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Actress Christina Applegate has revealed that she has MS, a neurological autoimmune disease. Photo courtesy of Mike Coppola via CNN.

49-year-old actress Christina Applegate revealed on Twitter this week that she has been diagnosed with multiple sclerosis (MS), an autoimmune disease affecting the central nervous system. Applegate says she was diagnosed “a few months ago” after experiencing symptoms of the disease.

Commenting on her diagnosis, she said: “It’s been a strange journey. But I have been so supported by people that I know who also have this condition. It’s been a tough road…but as we all know, the road keeps going.”

According to John Hopkins Medicine, multiple sclerosis occurs when the immune system attacks nerve fibers and the myelin sheath – a fatty substance which insulates healthy nerve fibers – in the brain and spinal cord. This attack causes inflammation, which destroys nerve cell processes and myelin, altering electrical messages in the brain.

There are different types of MS, the most common of which is relapsing-remitting multiple sclerosis, which affects 90% of those diagnosed. Symptoms of a multiple sclerosis relapse include: fatigue, numbness, tingling, blurred vision, unsteady gait, and weakness.

Worldwide, more than 2.3 million people live with MS, including almost 1 million adults in the United States alone, according to the National MS Society. The neurological autoimmune disease can be disabling, although the MS Society states that the majority of people with the condition do not become severely disabled. Two-thirds of people who have MS remain able to walk, though they may need a mobility aid, such as a cane, and some will use a scooter or wheelchair because of fatigue, weakness, balance problems, or to assist with conserving energy. 

Since coming out as newly diagnosed with MS, Applegate has received an outpouring of support from fans and other celebrities with the disease. Fellow actress Selma Blair, who co-starred with Applegate in a romantic comedy in 2002 and also has multiple sclerosis, tweeted: “Loving you always. Always here. As are our kids. Beating us up with love.” Talk show host Montel Williams, who also has MS, also tweeted his support: “We have MS – it will never have us unless we let it. Tara and I are sending hope and light your way.”

MS isn’t the first health battle Applegate has faced. In 2008, the star revealed that she had had a double mastectomy after testing posting for the BRCA gene, pre-disposing her to breast cancer. Facing her new MS diagnosis, Applegate has requested “privacy…as I go through this.”

Berkeley Alumni Create Startup Focused on Autoimmune Disease Therapies

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Geo Guillen, Marco Lobba, and Matthew Francis, the co-founders of autoimmune disease biotechnology company Catena Biosciences. Image courtesy of Berkeley News.

Marco Lobba was pursuing his PhD in Chemistry at UC Berkeley when he and his lab partners made a discovery. He had been studying the modification of proteins when he happened upon a technique called “oxidative coupling,” which modifies proteins so that they can be fused together. He and his partners also found that the enzyme tyrosinase could be used to make oxidative coupling much faster and more efficient. Tyrosinase is a naturally-occurring enzyme, found in fruits and vegetables, and is responsible for turning apples and avocadoes brown as they ripen.

The accelerated oxidative coupling method could be used to fuse proteins together, faster and more selectively, than any other method currently in use. This opens the door to treating autoimmune diseases, which attack the body by convincing a person’s antibodies to attack their own healthy cells. Using this discovery, scientists can attach ‘safe’ signals to healthy cells, helping the body’s immune system identify its own cells and refrain from attacking them.

“Think of it almost like Pavlov’s dogs,” explains Lobba. “Or tricking children into eating their vegetables by covering them in cheese,” he elaborated. “If you present the immune system with something it likes — at the same time as something it is attacking — it starts to associate that target as a good thing.”

Lobba presented his discovery during a course on entrepreneurship at UC Berkeley’s Haas School of Business. During the presentation, fellow classmate Geo Guillen saw how passionate he was about his research, and the value of his discovery in the treatment of autoimmune disease. It was this purpose that drove the pair to work together alongside Berkeley Chemistry professor, Matthew Francis, to co-found a startup called Catena Biosciences, focused on making autoimmune disease therapies.

Their startup launched remotely during the COVID-19 pandemic, at a time when biotechnology and pharmaceutical companies have come into focus for the role their organizations play in helping to keep our communities healthy and thriving. The startup has been valued at $10 million for its innovative technology and ground-breaking research.

Guillen commented on his company’s founding, saying: “We identified that the autoimmune market is one that is particularly ripe for disruption because a lot of the approaches to treating autoimmune disease focus on the symptoms, instead of the root cause. It’s a pretty large, untapped market.”

Catena Biosciences is aiming to conduct pre-clinical trials by the end of August 2021, which will test the impact of their therapeutics on autoimmune disease reactions in patients. Next month, the company will be looking to raise more funds for their startup to help them commercialize the treatment. The founders’ hope is that they can have a positive impact on those living with autoimmune diseases, like multiple sclerosis, lupus, and Type 1 diabetes.

The company has been awarded the 2021 Berkeley Big Ideas Award for their entrepreneurial endeavors. To learn more about Catena Biosciences, read about the company on the Berkeley News blog.