The physicality of our life leads with our brain as a fundamental vehicle of our minds. We can though reverse this process, as our mind can also lead our brain. Thanks Helen, JZ.
Helen Yu
Saturday, May 21, 2022
HOW TO TRAIN YOUR BRAIN
The physicality of our life leads with our brain as a fundamental vehicle of our minds. We can though reverse this process, as our mind can also lead our brain. Thanks Helen, JZ.
Helen Yu
Saturday, April 23, 2022
Friday, April 22, 2022
Anne-Sophie Mutter, Daniel Barenboim, Yo-Yo Ma – Beethoven: Triple Conce...
Beethoven: Triple Concerto in C Major, Op. 56 No. 2
Three classical music giants, Anne-Sophie Mutter, Yo-Yo Ma and Daniel Barenboim celebrate the 250th anniversary of Beethoven’s birth by recording the Triple Concerto. Pairing the Concerto with the Seventh Symphony, the album also marks the 20th birthday of the West-Eastern Divan Orchestra.
The Triple Concerto has a special place in Beethoven’s oeuvre, revealing his revolutionary spirit and ingrained humour both in its sophisticated architecture and in its musical idiom. Ever inventive, creative and original, here Beethoven stages a lavish musical feast over-flowing with melody, a feast. Yo-Yo Ma puts it in these words: “For me, in the Triple Concerto, it’s the constant invention that always takes me by surprise. You know what I love about the piece? It’s so celebratory, so positive.” Performed by three of today’s most renowned classical artists and Beethoven interpreters – Anne-Sophie Mutter, Yo-Yo Ma and Daniel Barenboim and accompanied by the acclaimed West-Eastern Divan Orchestra. Watch them perform Beethoven's Triple Concerto in C Major, Op. 56, No.2 Largo – Attacca, Live at Philharmonie, Berlin (2019).
Anne-Sophie Mutter, Daniel Barenboim, Yo-Yo Ma – Beethoven: Triple Concerto C Major, Op. 56, No. 2
Listen to the Triple Concerto: https://DG.lnk.to/TripleConcerto
Subscribe here – The Best Of Classical Music: http://bit.ly/Subscribe_DG
https://youtu.be/452nsCCzIJs
Thursday, April 14, 2022
2022 Pathways to Wellness in MS: Nutrition
Pathways Programs
Virtual Discussions
2021 Pathways to Wellness in MS Program
2022 Pathways to Wellness in MS: Nutrition
Virtual Program
This Pathways to Wellness in MS program, focused on nutrition, empowers people affected by MS to solve wellness challenges. Get up to speed on current research intersections of diet and MS, healthy nutrition and how to eat well, and the benefits of taking a comprehensive wellness approach to positively impact your quality of life. Don't miss this opportunity to connect with others in the MS community through this unique virtual experience.
Pathways to Wellness in MS: Nutrition took place on March 31. The three general sessions are accessible on-demand now in the virtual environment, and the three breakout sessions will be available soon. Login or register to view this program today!Log In Now
General Sessions Available On Demand
The Science Behind MS Nutrition
Dietary MS research studies are the foundation of leveraging nutrition to feel your best. Learn more about those studies to understand outcomes, explore common co-morbidities, and how nutrition can play a role in your multiple sclerosis and your overall health.
Watch Video
Eating Well with MS
Eating well doesn't have to be complicated, and starts with understanding the types of food that make your body feel its best. Learn strategies to build a healthy meal, interpret nutrition food labels and have more confidence in your daily dietary choices. Start eating well with MS today!
Watch Video
Nutrition: A Comprehensive Approach
Wellness is most successful as a well-rounded approach with different but equally important parts. Good nutrition is a key piece, in addition to physical wellness like exercise, emotional well-being through stress management and developing healthy relationships with support systems.
Watch Video
Breakout Sessions Coming Soon
How to Get the Most Out of this Program
Personalize your learning experience to get what you want and need out of this program.
Attend three general sessions and join the breakout topic of your choice
Engage with other attendees in the environment and session chats
Visit the Connection Lounge, Wellness Center and Resource Room
Participate in activities and demonstration videos during program breaks We hope to see you virtually on March 31! In the meantime, please reference our 2021 Pathways to Wellness in MS program sessions and worksheets focused on exercise and lifestyle physical activity or join a virtual discussion group to hear from trusted Comprehensive MS Care Centers and connect with others in the MS community.
Resources
Diet and Nutrition: Eating healthy can help manage MS symptoms. Learn about dietary research and evidence-based recommendations.
Living Well with MS: See how a healthy diet, regular exercise, stress management and other wellness strategies can help you manage your symptoms and feel your best.
Dietary Studies in MS: while current research is limited, researchers are beginning to make significant connections around diet and MS
National MS Society Community in Facebook: access learning guides and engage in open discussions with others who have similar interests in a supportive environment.
Sponsors
We would like to thank all our 2022 program sponsors.
Pathways to Wellness in MS: Nutrition is funded in part in memory of Dr. Jean Griswold.
Thursday, April 14, 2022
New Study Confirms the High Costs of MS to Individuals and the U.S. Economy -- ("The Economic Burden of Multiple Sclerosis in the U.S.")
April 13, 2022
A new study, commissioned by the National MS Society, shows that for the nearly 1 million people living with MS in the U.S., the average total cost of living with multiple sclerosis is $88,487 per year, underscoring what many people affected by MS know all too well – MS is a highly expensive disease. The total estimated cost to the U.S. economy, including government, industry and individuals, is $85.4 billion per year.
Direct medical costs such as doctor’s appointment and medications are the biggest contributor to the high cost, with disease-modifying therapies (DMTs) being the biggest cost of living with the disease. The medical costs associated with living with MS are $65,612 more each year than medical costs for individuals who do not have MS. The actual amount spent per year varies from person to person based on many factors, including use of DMTs, daily life needs and health insurance coverage. The study also factored indirect and non-medical costs, such as costs of daily living, early forced retirement, home modifications and more. Carepartners pay an average of $4,333 each year to provide care to someone living with MS.
“While we’ve long known MS is a highly expensive disease, this study confirms the real impact these costs have on people with MS, their families and carepartners—as well as the U.S. economy. Urgent and immediate action is needed to ensure the cost of care is affordable and treatment for MS is accessible,” said Cyndi Zagieboylo, the National MS Society’s President and CEO. “It’s important to thank the nearly 1,000 people affected by MS who gave their time to be a part of this study so we can accurately understand their experience and the financial challenges this disease has brought to their lives.”
Learn more about the cost of living with multiple sclerosis and resources to help.
Details of the Study
To estimate the national economic cost of MS, researchers reviewed health claims data from Medicare and private insurer sources, and mortality data. They also conducted a survey of 946 people living with MS. The investigators compared costs between people with MS and matched people without MS.
The team found that of the overall annual cost to the U.S. economy of $85.4 billion, $63.3 billion was in direct medical costs such as prescription drugs. Nearly $22.1 billion was in indirect or non-medical costs, including productivity loss, caregiver costs, and lost earnings.
On an individual level, medical costs, especially DMTs, were the biggest cost of living with MS. The medical costs associated with living with MS are $65,612 more each year than medical costs for individuals who do not have MS. The annual costs to individuals on an MS disease-modifying therapy ranged from $57,202 to $92,719, depending on their age and gender.
Key Points
The National MS Society commissioned this study to better understand the financial burden of MS on people with MS, their families and the U.S. economy. While we have long understood that MS is an expensive disease, having data can help identify the most significant factors and direct our advocacy efforts to propel policy changes.
The National MS Society is committed to ensuring people with MS have access to personalized, affordable, high-quality healthcare. The medical costs associated with living with MS are $65,612 more each year than for individuals who do not have MS, with the biggest medical cost being disease-modifying therapies. The Society is currently advocating for policies to reduce high prescription drug costs and helping people with MS afford high-quality health insurance, learn more here. Watch the Society’s Vice President of Advocacy, Steffany Stern's testimony before the Senate Finance Committee and learn more about how to be an MS Activist.
People with MS are protected from discrimination under the Americans with Disabilities Act (ADA). If you are experiencing financial or employment challenges related to MS, the National MS Society can help connect you to the information, resources and support you need.
Connect with an MS Navigator by emailing contactusnmss@nmss.org or calling 800-344-4867
Get the Financial and Insurance Information you need
Learn when and how to appeal an insurance decision
Guide to prescription financial assistance
Learn more about your employment rights and how to request accommodations
“The Economic Burden of Multiple Sclerosis in the U.S.: Estimate of Direct and Indirect Costs,” by Bruce Bebo, Inna Cintina, Nicholas LaRocca, Leslie Ritter, Bari Talente, Daniel Hartung, Surachat Ngorsuraches, Mitchell Wallin, and Grace Yang, was published online on April 13, 2022 in Neurology®, the medical journal of the American Academy of Neurology.
About Multiple Sclerosis
Multiple sclerosis is an unpredictable disease of the central nervous system. Currently there is no cure. Symptoms vary from person to person and may include disabling fatigue, mobility challenges, cognitive changes, and vision issues. An estimated 1 million people live with MS in the United States. Early diagnosis and treatment are critical to minimize disability. Significant progress is being made to achieve a world free of MS.
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New Study Confirms the High Costs of MS to Individuals and the U.S. Economy | National Multiple Sclerosis Society (nationalmssociety.org)
Wednesday, March 16, 2022
Marginal Gains Philosophy
Start promoting the marginal gains philosophy to the management of MS, which is based on Sir David Brailsford's approach to competitive cycling and is one of the reasons why the British cycling teams has been so dominant in the last two decades.
“The whole principle came from the idea that if you broke down everything you could think of that goes into riding a bike, and then improved it by 1%, you will get a significant increase when you put them all together.” ……. Sir David Brailsford
Monday, January 31, 2022
How Epstein-Barr virus triggers multiple sclerosis
A new study found that part of the Epstein-Barr virus mimics a protein made in the brain and spinal cord, leading the immune system to mistakenly attack the body’s nerve cells.
January 24, 2022 - By Hadley Leggett
William Robinson is the senior author of a paper that demonstrated how a common herpes virus can trigger multiple sclerosis by priming the immune system to attack the nervous system.
Steve Fisch
Scientists have long suspected — but failed to prove — a link between certain viral infections and the development of multiple sclerosis, a crippling autoimmune disease that affects nearly 1 million Americans. Now, a study led by Stanford Medicine researchers has proved that the Epstein-Barr virus, a common type of herpes virus, triggers multiple sclerosis by priming the immune system to attack the body’s own nervous system.
The study, published Jan. 24 in Nature, shows that approximately 20% to 25% of patients with multiple sclerosis have antibodies in their blood that bind tightly to both a protein from the Epstein-Barr virus, called EBNA1, and a protein made in the brain and spinal cord, called the glial cell adhesion molecule, or GlialCAM.
“Part of the EBV protein mimics your own host protein — in this case, GlialCAM, found in the insulating sheath on nerves,” said William Robinson, MD, PhD, professor of immunology and rheumatology at Stanford. “This means that when the immune system attacks EBV to clear the virus, it also ends up targeting GlialCAM in the myelin.”
Myelin forms the protective coating around nerve cells, and when it’s damaged, electrical impulses can no longer jump efficiently from one nerve to the next, resulting in the numbness, muscle weakness and severe fatigue of multiple sclerosis.
The lead author of the study is Stanford research scientist Tobias Lanz, MD. The senior author is Robinson, the James. W. Raitt Professor, who credited co-author Lawrence Steinman, MD, professor of neurology at Stanford, with also playing a key role in driving the research.
“This is the first time anyone has shown rather definitively that a virus is the trigger for multiple sclerosis,” Steinman said. “And these exciting findings open up some new directions for clinical trials in MS treatment.”
MS and viruses: an elusive connection
Previous research has shown that multiple sclerosis patients have increased antibodies to a variety of common viruses, including measles, mumps, varicella-zoster and Epstein-Barr virus. In fact, more than 99% of MS patients have EBV antibodies in their blood, indicating a prior infection, compared with 94% of healthy individuals. But despite this epidemiologic correlation, scientists have struggled to prove a causal connection.
“Nobody really knows what causes autoimmune diseases, and for many decades, all sorts of different viruses have been hypothesized,” Robinson said. “But when people did further mechanistic digging, everything fell apart, and it turned out that getting those other viruses didn’t actually cause MS.”
This is the first time anyone has shown rather definitively that a virus is the trigger for multiple sclerosis.
To search for this elusive mechanistic link, the researchers started by examining the antibodies produced by immune cells in the blood and spinal fluid of nine MS patients. Unlike in healthy individuals, the immune cells of MS patients traffic to the brain and spinal cord, where they produce large amounts of a few types of antibodies. Patterns of these antibody proteins, called oligoclonal bands, are found during analysis of the spinal fluid and are part of the diagnostic criteria for MS.
“No one knows exactly what those antibodies bind to or where they’re from,” Robinson said. “So the first thing we did was analyze the antibodies from the oligoclonal bands, and showed that they come from B cells in the spinal fluid.”
B cells are a type of white blood cell made in the bone marrow, and the technology to sequence these cells individually was developed by the Robinson lab about eight years ago. “In the past, researchers would take serum and spinal fluid from MS patients and test them on planar arrays or throw them on histology slides to see what sticks,” Lanz said. “What we did was a different approach: We took B cells from the spinal fluid, single-cell sorted them and sequenced each one separately. In a single-cell format and at the scale of tens to hundreds of B cells per patient, that had not been done before.”
MS antibodies bind viral protein EBNA1
Once the researchers determined that the oligoclonal bands in MS are produced by the sorted B cells in the spinal fluid, they expressed individual antibodies from these cells and tested them for reactivity against hundreds of different antigens.
“We started with human antigens,” Robinson said, “but couldn’t find clear reactivity. So eventually we tested them against EBV and other herpes viruses, and lo and behold, several of these antibodies, and one in particular, bound to EBV.”
Six of the nine MS patients had antibodies that bound to the EBV protein EBNA1, and eight of nine had antibodies to some fragment of EBNA1. The researchers focused on one antibody that binds EBNA1 in a region known to elicit high reactivity in MS patients. They were then able to solve the crystal structure of the antibody-antigen complex, to determine which parts were most important for binding.
Before this discovery, Robinson said he’d been unconvinced that EBV caused MS. “We all thought it was just kind of an artifact; we didn’t really think it was causative. But when we found these antibodies that bound EBV in the spinal fluid, produced by the spinal fluid B cells, it made us revisit the potential association that we’d dismissed.”
Molecular mimicry provides mechanism for development of MS
Next, the researchers tested the same antibody on a microarray containing more than 16,000 human proteins. When they discovered that the antibody also bound with high affinity to GlialCAM, they knew they’d found a specific mechanism for how EBV infection could trigger multiple sclerosis.
“EBV tricks the immune system into responding not only to the virus, but also to this critical component of the cells that make up the white matter in our brains,” Steinman said. “To use a military metaphor, it’s like friendly fire: In fighting the virus, we damage our own army.”
To find out what percentage of MS might be caused by this so-called “molecular mimicry” between EBNA1 and GlialCAM, the researchers looked at a broader sample of MS patients and found elevated reactivity to the EBNA1 protein and GlialCAM in 20% to 25% of blood samples in three separate MS cohorts.
“Twenty-five percent is a conservative number,” Robinson said, noting that it doesn’t include patients who may have previously reacted to GlialCAM following EBV infection but whose immune response has evolved since the initial trigger.
In fact, a study of 801 MS cases from more than 10 million active-duty military personnel over 20 years found that EBV infection was present in all but one case at the time of MS onset. A paper describing that study, published this month in Science, found that of 35 people who were initially EBV-negative, all but one became infected with EBV before the onset of MS. In addition, this separate group of researchers identified the same EBNA1 region as a major antibody target in MS patients. Together with the discovery of EBNA1/GlialCAM cross-reactivity, this data provides compelling evidence that EBV is the trigger for the vast majority of MS cases, as Robinson and Steinman point out in a Science Perspective, also published in January.
Mouse models provide further proof
In work guided by co-author and senior research scientist Peggy Ho, the importance of the anti-EBNA1 immune response was further assessed by using a common mouse model of MS called experimental autoimmune encephalomyelitis. After receiving an injection of a fragment of the EBNA1 protein, the mice exhibited more severe paralysis, more immune cells invading their central nervous system, and more damage to the protective coating on their nerve cells, compared with mice injected with a control protein fragment.
“It’s just further connecting the dots,” Robinson said. “If you immunize a mouse with a particular antigen and it makes paralysis worse, it suggests that an immune response against that target can contribute to MS pathogenesis.”
Paving the way for future MS treatments
Perhaps the most exciting aspect of this discovery is its potential to create new pathways for the clinical treatment of multiple sclerosis. “If a virus is the target of the immune response that’s going an unwanted way in the MS brain, why not get rid of the virus?” Steinman said, noting that a vaccine against Epstein-Barr virus could perhaps eventually eradicate MS, in the same way polio was eradicated from the United States in the 1970s.
But this research also demonstrates why manufacturers would need to be extra careful in selecting which antigens to incorporate into an EBV vaccine. “You don’t want to choose those antigens, like EBNA1, that could cause autoimmunity,” Lanz said.
In addition, an EBV vaccine wouldn’t necessarily help patients who have already developed EBNA1/GlialCAM cross-reactivity. For those patients, a better option might be to “tolerize” the immune system so it no longer responds to GlialCAM, Steinman said. “There are two promising technologies here, one involving a reverse vaccine using DNA plasmids and another using RNA technology from the same company in Germany that made the Pfizer vaccine for COVID-19.”
The discovery of how EBV triggers multiple sclerosis could also have ramifications for research into other autoimmune diseases, such as lupus and rheumatoid arthritis, which, like MS, have been significantly associated with EBV infection in epidemiologic studies.
Robinson is a member of Stanford Bio-X, Wu Tsai Human Performance Alliance at Stanford, the Stanford Maternal and Child Health Research Institute, and the Stanford Cancer Institute. Steinman is a member of Stanford Bio-X, the Stanford Maternal and Child Health Research Institute, and the Wu Tsai Neurosciences Institute at Stanford.
Other Stanford co-authors of the Nature paper are graduate students Camille Brewer and Manasi Iyer; postdoctoral scholars Jae Seung Moon, PhD, and Alejandro Gomez, PhD; research specialist Kevin Jude; director of crystallography Daniel Fernandez; former postdoctoral scholar Ricardo Fernandes, PhD; former visiting scientist Gabriel-Stefan Nadj, MD; assistant professor of neurosurgery Bradley Zuchero, PhD; clinical professor of neurology Jeffrey Dunn, MD; clinical associate professor of neurology and neurological sciences Christopher Lock, MBBS, PhD; clinical assistant professor of neurology and neurological sciences Lucas Kipp, MD; and professor of molecular and cellular physiology Christopher Garcia, PhD.
Researchers from the University of Heidelberg, Germany; the Howard Hughes Medical Institute; UC San Francisco; the NYU Grossman School of Medicine; the SLAC National Accelerator Laboratory; the Institute of Experimental Immunology in Lubeck, Germany; Atara Biotherapeutics Inc.; and the University of Oxford, UK, also contributed to the work.
The study was funded by grants from the National Institutes of Health (R01 AR063676, U19 AI110491, 1S10OD010582-01A1 and GIGMS P30GM133894), the Juvenile Diabetes Research Foundation, the Lupus Research Alliance, the German Research Foundation, Atara Biotherapeutics Inc., the NYU Grossman School of Medicine and the U.S. Department of Energy.
https://med.stanford.edu/news/all-news/2022/01/epstein-barr-virus-multiple-sclerosis.html
January 24, 2022 - By Hadley Leggett
William Robinson is the senior author of a paper that demonstrated how a common herpes virus can trigger multiple sclerosis by priming the immune system to attack the nervous system.
Steve Fisch
Scientists have long suspected — but failed to prove — a link between certain viral infections and the development of multiple sclerosis, a crippling autoimmune disease that affects nearly 1 million Americans. Now, a study led by Stanford Medicine researchers has proved that the Epstein-Barr virus, a common type of herpes virus, triggers multiple sclerosis by priming the immune system to attack the body’s own nervous system.
The study, published Jan. 24 in Nature, shows that approximately 20% to 25% of patients with multiple sclerosis have antibodies in their blood that bind tightly to both a protein from the Epstein-Barr virus, called EBNA1, and a protein made in the brain and spinal cord, called the glial cell adhesion molecule, or GlialCAM.
“Part of the EBV protein mimics your own host protein — in this case, GlialCAM, found in the insulating sheath on nerves,” said William Robinson, MD, PhD, professor of immunology and rheumatology at Stanford. “This means that when the immune system attacks EBV to clear the virus, it also ends up targeting GlialCAM in the myelin.”
Myelin forms the protective coating around nerve cells, and when it’s damaged, electrical impulses can no longer jump efficiently from one nerve to the next, resulting in the numbness, muscle weakness and severe fatigue of multiple sclerosis.
The lead author of the study is Stanford research scientist Tobias Lanz, MD. The senior author is Robinson, the James. W. Raitt Professor, who credited co-author Lawrence Steinman, MD, professor of neurology at Stanford, with also playing a key role in driving the research.
“This is the first time anyone has shown rather definitively that a virus is the trigger for multiple sclerosis,” Steinman said. “And these exciting findings open up some new directions for clinical trials in MS treatment.”
MS and viruses: an elusive connection
Previous research has shown that multiple sclerosis patients have increased antibodies to a variety of common viruses, including measles, mumps, varicella-zoster and Epstein-Barr virus. In fact, more than 99% of MS patients have EBV antibodies in their blood, indicating a prior infection, compared with 94% of healthy individuals. But despite this epidemiologic correlation, scientists have struggled to prove a causal connection.
“Nobody really knows what causes autoimmune diseases, and for many decades, all sorts of different viruses have been hypothesized,” Robinson said. “But when people did further mechanistic digging, everything fell apart, and it turned out that getting those other viruses didn’t actually cause MS.”
This is the first time anyone has shown rather definitively that a virus is the trigger for multiple sclerosis.
To search for this elusive mechanistic link, the researchers started by examining the antibodies produced by immune cells in the blood and spinal fluid of nine MS patients. Unlike in healthy individuals, the immune cells of MS patients traffic to the brain and spinal cord, where they produce large amounts of a few types of antibodies. Patterns of these antibody proteins, called oligoclonal bands, are found during analysis of the spinal fluid and are part of the diagnostic criteria for MS.
“No one knows exactly what those antibodies bind to or where they’re from,” Robinson said. “So the first thing we did was analyze the antibodies from the oligoclonal bands, and showed that they come from B cells in the spinal fluid.”
B cells are a type of white blood cell made in the bone marrow, and the technology to sequence these cells individually was developed by the Robinson lab about eight years ago. “In the past, researchers would take serum and spinal fluid from MS patients and test them on planar arrays or throw them on histology slides to see what sticks,” Lanz said. “What we did was a different approach: We took B cells from the spinal fluid, single-cell sorted them and sequenced each one separately. In a single-cell format and at the scale of tens to hundreds of B cells per patient, that had not been done before.”
MS antibodies bind viral protein EBNA1
Once the researchers determined that the oligoclonal bands in MS are produced by the sorted B cells in the spinal fluid, they expressed individual antibodies from these cells and tested them for reactivity against hundreds of different antigens.
“We started with human antigens,” Robinson said, “but couldn’t find clear reactivity. So eventually we tested them against EBV and other herpes viruses, and lo and behold, several of these antibodies, and one in particular, bound to EBV.”
Six of the nine MS patients had antibodies that bound to the EBV protein EBNA1, and eight of nine had antibodies to some fragment of EBNA1. The researchers focused on one antibody that binds EBNA1 in a region known to elicit high reactivity in MS patients. They were then able to solve the crystal structure of the antibody-antigen complex, to determine which parts were most important for binding.
Before this discovery, Robinson said he’d been unconvinced that EBV caused MS. “We all thought it was just kind of an artifact; we didn’t really think it was causative. But when we found these antibodies that bound EBV in the spinal fluid, produced by the spinal fluid B cells, it made us revisit the potential association that we’d dismissed.”
Molecular mimicry provides mechanism for development of MS
Next, the researchers tested the same antibody on a microarray containing more than 16,000 human proteins. When they discovered that the antibody also bound with high affinity to GlialCAM, they knew they’d found a specific mechanism for how EBV infection could trigger multiple sclerosis.
“EBV tricks the immune system into responding not only to the virus, but also to this critical component of the cells that make up the white matter in our brains,” Steinman said. “To use a military metaphor, it’s like friendly fire: In fighting the virus, we damage our own army.”
To find out what percentage of MS might be caused by this so-called “molecular mimicry” between EBNA1 and GlialCAM, the researchers looked at a broader sample of MS patients and found elevated reactivity to the EBNA1 protein and GlialCAM in 20% to 25% of blood samples in three separate MS cohorts.
“Twenty-five percent is a conservative number,” Robinson said, noting that it doesn’t include patients who may have previously reacted to GlialCAM following EBV infection but whose immune response has evolved since the initial trigger.
In fact, a study of 801 MS cases from more than 10 million active-duty military personnel over 20 years found that EBV infection was present in all but one case at the time of MS onset. A paper describing that study, published this month in Science, found that of 35 people who were initially EBV-negative, all but one became infected with EBV before the onset of MS. In addition, this separate group of researchers identified the same EBNA1 region as a major antibody target in MS patients. Together with the discovery of EBNA1/GlialCAM cross-reactivity, this data provides compelling evidence that EBV is the trigger for the vast majority of MS cases, as Robinson and Steinman point out in a Science Perspective, also published in January.
Mouse models provide further proof
In work guided by co-author and senior research scientist Peggy Ho, the importance of the anti-EBNA1 immune response was further assessed by using a common mouse model of MS called experimental autoimmune encephalomyelitis. After receiving an injection of a fragment of the EBNA1 protein, the mice exhibited more severe paralysis, more immune cells invading their central nervous system, and more damage to the protective coating on their nerve cells, compared with mice injected with a control protein fragment.
“It’s just further connecting the dots,” Robinson said. “If you immunize a mouse with a particular antigen and it makes paralysis worse, it suggests that an immune response against that target can contribute to MS pathogenesis.”
Paving the way for future MS treatments
Perhaps the most exciting aspect of this discovery is its potential to create new pathways for the clinical treatment of multiple sclerosis. “If a virus is the target of the immune response that’s going an unwanted way in the MS brain, why not get rid of the virus?” Steinman said, noting that a vaccine against Epstein-Barr virus could perhaps eventually eradicate MS, in the same way polio was eradicated from the United States in the 1970s.
But this research also demonstrates why manufacturers would need to be extra careful in selecting which antigens to incorporate into an EBV vaccine. “You don’t want to choose those antigens, like EBNA1, that could cause autoimmunity,” Lanz said.
In addition, an EBV vaccine wouldn’t necessarily help patients who have already developed EBNA1/GlialCAM cross-reactivity. For those patients, a better option might be to “tolerize” the immune system so it no longer responds to GlialCAM, Steinman said. “There are two promising technologies here, one involving a reverse vaccine using DNA plasmids and another using RNA technology from the same company in Germany that made the Pfizer vaccine for COVID-19.”
The discovery of how EBV triggers multiple sclerosis could also have ramifications for research into other autoimmune diseases, such as lupus and rheumatoid arthritis, which, like MS, have been significantly associated with EBV infection in epidemiologic studies.
Robinson is a member of Stanford Bio-X, Wu Tsai Human Performance Alliance at Stanford, the Stanford Maternal and Child Health Research Institute, and the Stanford Cancer Institute. Steinman is a member of Stanford Bio-X, the Stanford Maternal and Child Health Research Institute, and the Wu Tsai Neurosciences Institute at Stanford.
Other Stanford co-authors of the Nature paper are graduate students Camille Brewer and Manasi Iyer; postdoctoral scholars Jae Seung Moon, PhD, and Alejandro Gomez, PhD; research specialist Kevin Jude; director of crystallography Daniel Fernandez; former postdoctoral scholar Ricardo Fernandes, PhD; former visiting scientist Gabriel-Stefan Nadj, MD; assistant professor of neurosurgery Bradley Zuchero, PhD; clinical professor of neurology Jeffrey Dunn, MD; clinical associate professor of neurology and neurological sciences Christopher Lock, MBBS, PhD; clinical assistant professor of neurology and neurological sciences Lucas Kipp, MD; and professor of molecular and cellular physiology Christopher Garcia, PhD.
Researchers from the University of Heidelberg, Germany; the Howard Hughes Medical Institute; UC San Francisco; the NYU Grossman School of Medicine; the SLAC National Accelerator Laboratory; the Institute of Experimental Immunology in Lubeck, Germany; Atara Biotherapeutics Inc.; and the University of Oxford, UK, also contributed to the work.
The study was funded by grants from the National Institutes of Health (R01 AR063676, U19 AI110491, 1S10OD010582-01A1 and GIGMS P30GM133894), the Juvenile Diabetes Research Foundation, the Lupus Research Alliance, the German Research Foundation, Atara Biotherapeutics Inc., the NYU Grossman School of Medicine and the U.S. Department of Energy.
https://med.stanford.edu/news/all-news/2022/01/epstein-barr-virus-multiple-sclerosis.html
Bob Dylan - Desolation Row (Los Angeles 1965, Second Ever Live Performance)
https://youtu.be/RlIeY7RUo4w
Friday, December 31, 2021
Symptoms
First symptoms
A common visual symptom of MS is optic neuritis — inflammation of the optic (vision) nerve. Optic neuritis usually occurs in one eye and may cause aching pain with eye movement, blurred vision, dim vision, or loss of color vision. of MS
- Blurred or double vision
- Red-green color distortion
- Pain and loss of vision because of swelling of the optic nerve (optic neuritis)
- Trouble walking and difficulty with balance
- An abnormal feeling, such as numbness, prickling, or pins and needles (paresthesia)
Other symptoms of multiple sclerosis
- Muscle weakness in the arms and legs
- Trouble with coordination. You may have problems walking or standing. You may also be partly or completely paralyzed.
- Spasticity. This is the involuntary increased tone of muscles leading to stiffness and spasms.
- Fatigue. This may be brought on by physical activity. But it may ease with rest. You may have constant tiredness that doesn't go away.
- Loss of feeling
- Speech problems
- Tremor
- Dizziness
- Hearing loss
- Bowel and bladder problems
- Depression
- Changes in sexual function
About 50% of all people with MS have thinking (cognitive) problems linked to the disease. The effects of these problems may be mild. Your healthcare provider may only find them after much testing. The problems may be with:
- Focusing (concentration)
- Attention
- Memory
- Poor judgment
Symptoms of MS are grouped as primary, secondary, or tertiary as described below:
Primary symptoms. These symptoms are a direct result of the destruction of myelin:
| Secondary symptoms. These are complications that may occur as a result of the primary symptoms, for example:
| Tertiary symptoms. These are social, job-related, and psychological problems:
|
The symptoms of MS may look like other health problems. Always talk with your healthcare provider for a diagnosis.
https://www.cedars-sinai.org/health-library/diseases-and-conditions/m/multiple-sclerosis-ms.html
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