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Study Questions Influence of High-Salt Diet on MS

SUMMARY

  • Some recent studies have suggested that high intake of salt in the diet might influence MS disease activity and progression, but other studies have not confirmed that link.
  • In work partly funded by the National MS Society, researchers took advantage of data accumulated from a previous clinical trial involving 465 people with possible early signs of MS (CIS) whose salt levels in urine were measured over the course of 5 years.
  • They found no connection between salt intake and MS activity.
  • The study, “Sodium Intake and Multiple Sclerosis Activity and Progression in BENEFIT,” was published in the July 2017 issue of the Annals of Neurology (2017;82:20-29).
  • Although this study does not support a link between high-salt diets and MS disease activity, research suggests that most Americans eat more salt than is recommended by federal guidelines. Reducing dietary salt is considered by most to be beneficial to the heart and circulatory system.

DETAILS
Background: Several recent studies have suggested that dietary salt (sodium chloride) could potentially influence MS disease activity and progression. For example, one study of 70 people with relapsing-remitting MS, who were followed for two years, found that higher levels of salt measured in urine samples were associated with a higher rate of relapses and larger brain MRI lesions. In addition, mice fed a high-salt diet developed a more aggressive course of EAE, a laboratory model of MS. But two studies in pediatric MS did not find a relationship between self-reported salt intake and MS risk or relapse rates. Resolving this question is important because it offers the possibility that reducing salt intake might improve a person’s overall health and their course of MS.

This Study: In work partly funded by the National MS Society, researchers set out to determine if a high-salt diet is associated with faster conversion from a first neurologic episode (known as clinically isolated syndrome or CIS) to a diagnosis of definite multiple sclerosis, or with MS disease activity. Kathryn C. Fitzgerald, ScD (Johns Hopkins School of Medicine), Alberto Ascherio, MD, DrPH (Harvard T. H. Chan School of Public Health) and colleagues took advantage of data accumulated from a previous clinical trial involving 465 participants who participated in a trial called BENEFIT (Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment) over 5 years. The trial compared benefits of giving interferon to individuals with CIS early versus later. Each person provided an average of 14 urine samples throughout the five-year follow-up. The researchers estimated average long-term sodium intake from the multiple urine samples, adjusting for age, sex, height, weight, where participants lived, and many other variables.

Results: Researchers found that neither average nor high urine sodium levels were associated with conversion to definite MS. They also weren’t associated with new MRI lesions at any point in the five years, relapse rates, or progression of disability. These results suggest that high sodium intake does not play a major role in influencing MS disease course or activity in people treated with interferon, at least in the early stages of the disease.

While the study has several strengths, including its length, large sample size, and systematic collection of data, it has limitations: BENEFIT participants were treated nearly uniformly with interferon, and the results may not apply to people on other therapies or no therapy. In addition, participants in the BENEFIT trial were primarily Caucasian and resided in Europe and Canada, and it isn’t known if similar results would apply to other populations and ethnicities. The results also don’t answer the question of whether salt intake affects the risk of developing MS in the first place.

The study, “Sodium Intake and Multiple Sclerosis Activity and Progression in BENEFIT,” was published in the July 2017 issue of the Annals of Neurology (2017;82:20-29).

Comment: Although this study does not support a link between high-salt intake and MS disease activity, research suggests that most Americans eat more salt than is recommended by federal guidelines. Even in the absence of direct evidence that MS immune activity is influenced by salt, reducing dietary salt is considered by most to be beneficial to the heart and circulatory system.

Read More: Diet, along with exercise, cognitive health, and other healthy behaviors can make a big difference to how you feel as you deal with MS. Learn more about living well with MS

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Researchers Recruiting People with Primary Progressive MS for Genetics Studies – Key to finding treatment options

Primary progressive MS is characterized by steadily worsening neurologic function from the onset of the disease. There are still many gaps in the knowledge we have about what differentiates relapsing-remitting from primary progressive MS, and the underlying mechanisms of primary progressive MS. The MS Genetics Group at the University of California San Francisco is recruiting people with primary progressive MS for a research study involving a one-time blood sample donation with the goal of identifying genetic factors driving the course of the disease. The team also is looking for people without MS who are not related to serve as controls. The team hopes to identify the major genetic factors that play a role in disease presentation and progression. Please note: you do not have to be located in or travel to California to participate. Everything for the study can be done remotely and is free of charge to participants.

Rationale: Specific subtle variations in the human genome are known to play a role in determining who is susceptible to developing multiple sclerosis, and may also influence the course of the disease. People living with MS can make a difference in studies searching for these genes by donating their DNA with a blood sample. Identifying the exact location and role of MS genes could help determine who is at risk for developing the disease and can provide clues to its cause, prevention, and lead to better treatments.

Details: Once an individual has completed the initial online intake form, they will receive a call from the study coordinator to discuss details and answer any questions. The consent form and health information privacy form can be signed electronically. Participants will then be emailed a link to two additional short online surveys and sent a blood-collection kit. The kit includes everything necessary for the blood draw, which can be taken to your local Quest Diagnostics Lab and returned in a prepaid envelope to the lab at UCSF. There is no cost to participants.

Contact: To participate or request additional information, please complete a brief intake survey.
OR you may contact UCSF directly:
Clinical Research Coordinator
UCSF Multiple Sclerosis Genetic Susceptibility Project
675 Nelson Rising Lane, Suite 235A, Box 3206
San Francisco, CA 94158
Email: msdb@ucsf.edu
Toll Free Phone: 1-866-MS-Genes (1-866-674-3637) or Office Phone: (415) 502-7202

 

Researchers Find That Immune B Cells from People with MS May Harm Nerve Cells

SUMMARY:

  • Researchers co-funded by the National MS Society have found that immune B cells obtained from the blood of people with relapsing-remitting MS secrete products that can be toxic to nerve cells grown in lab dishes.
  • This study offers new insight into how B cells may contribute to nervous system damage in MS.
  • The team is now conducting further studies to identify the toxic factor or factors secreted by the B cells, and when and how they may act in people with MS, and to answer questions such as whether they are unique to MS, whether they are also evident in people with progressive MS.
  • Drs Robert P Lisak, Joyce Benjamins (Wayne State University), Amit Bar-Or (McGill University and currently at University of Pennsylvania) and colleagues published their findings in the Journal of Neuroimmunology (2017 Aug 15;309:88-99, published online May 17)

DETAILS
Background: While scientists still don’t know what causes multiple sclerosis, they do know that immune-system attacks are involved, resulting in damage to the myelin that insulates nerve fibers and to nerve cells and fibers themselves. Immune T cells have typically been named as culprits, but it has become clear that immune B cells, another type of white blood cell, are also involved in MS. Research and studies on B cells, including early studies supported by the National MS Society, eventually led to successful clinical trials and approval of Ocrevus™ (ocrelizumab – Genentech, a member of the Roche Group) to treat people with primary progressive and relapsing-remitting MS. Ocrevus depletes certain B cells.

The Study: The current study builds on the researchers’ earlier findings that B cells from the blood of people with relapsing-remitting MS – but not blood from healthy individuals – are toxic to certain cells that build myelin. In this study, the team isolated B cells in the laboratory from the blood of 13 women and men with relapsing-remitting MS who were not receiving disease-modifying treatment or recent steroids, and 13 controls without MS.

The researchers found that products released by B cells from the people with MS were toxic to both rat and human nerve cells grown in lab dishes, while cells from the controls did not incur the same damage. The nerve cells died from apoptosis – a type of self-destruct program – and not, as might be expected, from cell disintegration, or from immunoglobulins (antibodies) that have been identified as culprits in the MS attack.

Drs Robert P Lisak, Joyce Benjamins (Wayne State University), Amit Bar-Or (McGill University and currently at University of Pennsylvania) and colleagues published their findings in the Journal of Neuroimmunology (2017 Aug 15;309:88-99, published online May 17). This study was supported by the National MS Society (USA), the Research Foundation of the MS Society of Canada, and others.

Next Steps: This study offers new insight into how B cells may contribute to nervous system damage in MS. The team is now conducting further studies to identify the toxic factor or factors secreted by the B cells, and when and how they may act in people with MS. They are using “proteomics” for this work, advanced technologies the can identify and quantify numerous molecules simultaneously, along with other approaches. They also plan to answer questions such as whether the toxic B cells are unique to MS or are found in other immune mediated disease, which subsets of B cells produce the toxic effects and whether they are also evident in people with progressive MS.

Read More
Learn more about research on the immune system in MS

New Research on Lemtrada Reveals Insights into the Cause of Potential Side Effects

Researchers in the U.K. have evaluated additional findings about the immune-system impacts of Lemtrada® (alemtuzimab, Sanofi Genzyme), a disease-modifying therapy for treating people with relapsing MS.

The team used data from phase 3 clinical trials submitted to the European Medicines Agency during the drug’s successful approval process. Some of this data was previously reported at medical meetings and in Lemtrada’s prescribing information.

Among their findings, they report that Lemtrada caused long-term reduction of specific immune cells (memory B and T cells, including regulatory T cells). They also found that the body rapidly repopulated an overabundance of immature B cells.

They propose that the blockade of memory B and T cells drives the beneficial effects of Lemtrada.

They also speculate that the known potential side effect for autoimmune thyroid disease and other autoimmune disorders may be triggered by the overabundance of immature B cells that occurs when there are few regulatory T cells to keep them in check.

Studies like this one, which reveal more information about a therapy’s mode of action, are important and may also lead to insights about how to reduce side effects.

Drs. Klaus Schmierer, David Baker and others at the Queen Mary University of London report their findings in JAMA Neurology, published online June 12, 2017.

Read the open-access paper in JAMA Neurology
Read about Lemtrada
Read more about treating MS

Lemtrada is a registered trademark of Sanofi Genzyme

Interesting Results…

Gene That Boosts Resistance to Malaria linked to Susceptibility to MS and Lupus in Sardinia

Researchers from Italy found a strong association between the gene that instructs the molecule “BAFF” and susceptibility to MS and lupus in studies of nearly 6,000 people in Sardinia. The BAFF gene is crucial to activation of immune B cells and is also associated with resistance to malaria. Malaria was common in Sardinia until it was eradicated in 1950. The rates of MS and certain immune-mediated diseases are high in Sardinia. Further research is necessary to confirm whether this high rate is related to BAFF, and whether MS could be treated by a therapy that targets BAFF.

Read more about this study from the Genetic Literacy Project

Read the scientific summary of the paper in The New England Journal of Medicine

Read more about efforts to end MS forever

 
 

Novel Protein Identified Inside Cells During MS Inflammation May Help Explain Nerve Damage

Researchers from the University of Alberta in Canada report that levels of Rab32 – a protein that directs traffic between cell organs – are increased in sites of active inflammation in brain tissue obtained from people with MS and in mouse models of MS-like disease. This increase was linked to the destruction of nerve cells. If the results are confirmed, this knowledge could explain part of the neurodegenerative process that leads to progression of disability in MS and could be a target for development of effective MS treatments.

Read more on ReliaWire
Read the open access paper in Journal of Neuroinflammation
Read more about Research to stop MS in its tracks

Study Finds That Some Family Members of People with MS Show Possible Early Signs of the Disease without Symptoms

Summary

  • As part of a large-scale “Genes & Environment in MS” (GEMS) study to understand factors that lead to the development of multiple sclerosis, researchers analyzed the genes and backgrounds of individuals who had no symptoms of MS, but who had close family members with MS.
  • Based on that analysis, researchers identified a group of 40 women at higher risk for developing MS, and 25 women at lower risk. Extensive neurological testing and MRI scanning uncovered possible neurological abnormalities in the higher risk group, and MRI abnormalities in a small proportion of both groups.
  • “At this time, we are developing strategies to manage the risk of MS, but there is, as yet, no specific recommendation,” explains co-author Dr. Phillip De Jager. “Family members should be reassured that the vast majority of family members will not develop MS.”
  • The team (including Zongqi Xia, MD, PhD, of Brigham and Women’s Hospital, and Daniel S. Reich, MD, PhD, of National Institute of Neurological Disorders and Stroke, Bethesda, MD) has published results in JAMA Neurology (published online January 17, 2017).
  • This study was supported by the National MS Society and the National Institutes of Health, and the Society helped to recruit participants. Two of the study authors – Daniel S. Reich, MD, PhD, and Philip L. De Jager, MD, PhD – are winners of the prestigious Barancik Prize for Innovation in MS Research.

Background: An individual’s risk of developing MS increases if a close family member has MS. There is currently no way to predict which family members will develop MS. The goal of the Genes & Environment in MS (GEMS) study is to identify the genetic, environmental and immune profiles that may increase a person’s risk of developing MS.  Researchers are recruiting 5,000 subjects who have at least one first-degree relative with a diagnosis of MS. The GEMS Study is gathering genetic material (DNA) and environmental exposure history from participants as well as blood samples and brain magnetic resonance imaging (MRI) as an option. Investigators are classifying participants using the Genetic and Environmental Risk Score for MS Susceptibility (GERSMS), an experimental approach which incorporates genetic information and environmental exposures to identify people at higher or lower risk of developing MS.

The Study: As part of this large-scale, ongoing study, researchers looked at 65 women who are first-degree relatives of people with MS. The GERSMS indicated that 40 of these women were at higher risk of developing MS, and 25 women were at lower risk of developing MS. These women underwent a comprehensive neurologic examination and MRI scans.

Women in the higher risk group had less than normal vibration sensitivity in their big toes, a finding that indicates potential nerve dysfunction. A small percentage of the women in both groups had more MRI abnormalities associated with MS than one would expect to find in the general population.

The team (Zongqi Xia, MD, PhD, of Brigham and Women’s Hospital, Boston, MA, and Daniel S. Reich, MD, PhD, of National Institute of Neurological Disorders and Stroke, Bethesda, MD) has published results in JAMA Neurology (published online January 17, 2017).

This study was supported by the National MS Society and the National Institutes of Health, and the Society helped to recruit participants. Two of the study authors – Daniel S. Reich, MD, PhD, and Philip L. De Jager, MD, PhD – are winners of the prestigious Barancik Prize for Innovation in MS Research.

Next Steps:  In this study, women at high risk for MS showed possible early manifestations of the disease. “The goal of the Genes & Environment Study is to understand the sequence of events that leads someone to develop MS,” explains co-author Dr. De Jager. “At this time, we are developing strategies to manage the risk of MS, but there is, as yet, no specific recommendation. Family members should be reassured that the vast majority of family members will not develop MS.” He notes that the study did not test the possibility of preventive strategies, such as vitamin D supplementation.  “Taking vitamin D is good for bone health, and MS family members should discuss taking such supplements with their physician.”

Read more about research to find the genetic and environmental underpinnings of MS

 

New Study: Resilience in People with Chronic Disease is Linked to Social Satisfaction and Quality of Life – Not Physical Function

Summary

  • A survey of more than 1500 people with MS and other chronic diseases shows that resilience (the ability to solve problems and bounce back from difficult situations) is linked to satisfaction with social roles (such as work and family responsibilities) and quality of life, but not to physical function.
  • Understanding factors that promote resilience may help people with MS to not only cope with unpredictable changes in health and abilities, but to thrive in spite of these changes.  Learn more about how the resilience factor can help you to thrive. Watch an education program on Resilience: Addressing the Challenges of MS.
  • The team (Samuel Battalio, BS, and colleagues at the University of Washington) has published results in Archives of Physical Medicine and Rehabilitation (2016 Dec 16).

Background: Research on psychosocial issues forms a cornerstone of finding life-changing solutions for people with MS. MS can have a significant impact on a person’s emotions, not only because MS is unpredictable and challenging to live with, but because it affects parts of the brain that control mood. This study specifically looked at factors that can affect resilience (i.e., the ability tackle problems, find solutions and bounce back from difficult situations).

The Study: The team reviewed information on 1574 people with MS, muscular dystrophy, post poliomyelitis syndrome, and spinal cord injury, which was gathered from an ongoing survey that is tracking people in the United States who are aging with physical disabilities. Information was collected on resilience using a clinical scale, and on other factors (including physical function, satisfaction with social roles – meaning work and family responsibilities, and quality of life) using questionnaires that assess how people report their own health status.

The results suggest that people who reported significantly greater satisfaction with social roles and significantly greater quality of life had significantly higher resilience. This relationship was slightly different between men and women, in that men who expressed greater levels of satisfaction with social roles reported higher levels of resilience. Surprisingly, noted the authors, resilience was not significantly greater in people who reported better physical function.

The team (Samuel Battalio, BS, and colleagues at the University of Washington) has published results in Archives of Physical Medicine and Rehabilitation (2016 Dec 16).

Next Steps: The authors note that resilience is complex, and that further research could help uncover particular aspects of resilience that may be most beneficial to individuals.  Understanding factors that promote resilience may help people with MS to not only cope with unpredictable changes in health and abilities, but to thrive in spite of these changes.

There are behaviors that can help promote individuals’ resilience:

New Results Show that Magnetic Stimulation of Brain May Improve Working Memory and Brain Connectivity in People with MS

Summary

  • People with MS, but not healthy controls, showed improvements in working memory, brain activity, and “connectivity” (how parts of the brain interact with one another), after treatment with Repetitive Transcranial Magnet Stimulation (rTMS). This device generates electromagnet pulses that stimulate brain activity.
  • rTMS may have a future role in cognitive rehabilitation in people with MS, but further, larger studies are necessary to confirm the safety and effectiveness of this intervention and its long-term effects.
  • The team (Hanneke Hulst, MD, of VU Medical Center in Amsterdam, and others) has published results in Journal of Neurology, Neurosurgery, and Psychiatry (Published Online First: 14 December 2016).

Background: Repetitive Transcranial Magnet Stimulation (rTMS) was approved by the FDA as a treatment for major depression. A device that generates electromagnet pulses is placed on the scalp with the idea of stimulating specific brain activity. Studies have shown that people with MS who received rTMS showed significant decreases in depression. This team looked at whether rTMS improved working memory (short-term memory needed for tasks such as mental arithmetic), which can be affected in people with MS.

The Study: Investigators administered rTMS – or a “sham” version of lower intensity – to an area of the brain associated with working memory in17 people with MS and 11 healthy controls. None of the participants showed signs of impaired memory at the outset of the study. A potential adverse event of rTMS is seizures, so participants were excluded if they were taking medicine that put them at risk for seizures, or had MS brain lesions in particular areas. Before and after, participants underwent imaging and extensive neuropsychological testing aimed at investigating memory. They also completed a working memory task while undergoing functional MRI, which measures brain activity during tasks.

At the beginning of the study, there were no differences in working memory between people with MS and controls. After treatment, the results suggested improvements among people with MS in working memory, brain activity, and “connectivity” (how parts of the brain interact with one another). These changes were not seen in controls.

The team (Hanneke Hulst, MD, of VU Medical Center in Amsterdam, and others) has published results in Journal of Neurology, Neurosurgery, and Psychiatry

Next Steps: The authors comment that this small study implies that rTMS may play a future role in cognitive rehabilitation in people with MS. However, the study is limited by the small sample size and the fact that participants did not have obvious cognitive problems. Further studies that address these factors are necessary to confirm the safety and effectiveness of this intervention for people with MS and its long-term impact on day to day activities.

Read more about cognitive changes that affect people with MS

 

Positive Results Announced from Clinical Trial of BAF-312 (Siponimod) in Secondary Progressive MS

Summary

Results presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) provided additional details from a 60-month, phase III clinical trial of the experimental oral therapy siponimod (BAF312, Novartis Pharmaceuticals AG) involving 1,651 people with secondary progressive MS.

The trial met its primary endpoint of reducing the risk of disability progression compared with inactive placebo. Those on active treatment had a 21% reduced risk of disability progression compared to those on placebo. Secondary endpoints suggested that those on active therapy had 23.4% lower average change in brain volume and reduced lesion volume.

The therapy was generally well tolerated and similar to adverse events reported for similar compounds.

Details

Background: Siponimod (BAF312) is an experimental immune system-modulating therapy that was designed to be a more selective sphingosine 1-phosphate receptor modulator than Gilenya® (fingolimod, Novartis International AG). Gilenya, was approved in 2010 for adults with relapsing forms of MS to reduce the frequency of clinical relapses and to delay the accumulation of physical disability. Siponimod previously demonstrated safety and efficacy on MRI scans in a phase II study in people with relapsing-remitting MS (The Lancet Neurology, 2013 Aug;12(8):756-67).  Siponimod is thought to act by retaining certain white blood cells in the body’s lymph nodes, keeping them out of circulation and from entering the central nervous system. Siponimod also distributes effectively to the central nervous system (brain and spinal cord) where it may have direct anti-inflammatory or other effects.

The Study: Participants were randomly assigned to take siponimod or placebo capsules daily for up to 60 months. The primary endpoint of the study was reducing the risk of disability progression, as measured by the EDSS scale at three months. Secondary endpoints included reducing the risk of disability progression as measured by the EDSS at six months versus placebo, the risk of worsening mobility as measured by the timed 25-foot walk test, disease activity as observed on MRI scans, relapse rate, and safety/ tolerability.

Results:  Results were presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on September 17, 2016. The trial met its primary endpoint of reducing the risk of disability progression compared with inactive placebo. Those on active treatment had a 21% reduced risk of disability progression (confirmed at 3 months) compared to those on placebo. Secondary endpoints suggested that those on active therapy had at 26% reduced risk of disability progression (confirmed at 6 months), a 23.4% lower average change in brain volume, and reduced MRI-detected brain lesion volume. There was no significant difference seen between groups in the timed 25-foot walk. Relapse rates were significantly lower in those taking siponimod.

Safety: The therapy was generally well tolerated and similar to adverse events reported for similar compounds. Serious adverse events occurred in 16.7% of participants. The serious adverse events reported to be more likely for those taking siponimod included nervous system disorders and infections.

Comment:
“These results suggest a modest benefit for people with secondary progressive MS, which is a positive step forward in the global effort to speed solutions for people living with this chronic form of the disease,” said Timothy Coetzee, PhD, Chief Advocacy, Services and Research Officer at the National MS Society. “We look forward to learning additional details about its potential benefit and safety.”

Low-fat, plant-based diet in multiple sclerosis: A randomized controlled trial

Publication History

Published Online: July 06, 2016

http://www.msard-journal.com/article/S2211-0348(16)30100-6/fulltext#s0005

The role of diet in ameliorating the severity of multiple sclerosis (MS) has been long debated, but there remains a paucity of relevant research. Observational studies by Dr. Roy Swank, published between 1953 and 2003, suggested significantly reduced MS disease activity and disability progression and longer survival in people following a diet low in total and saturated fat compared with those who did not (Swank, 1953, Swank and Goodwin, 2003, Swank, 1970). Swank’s diet book, last published in 1987, remains popular among patients with MS. However, this approach to treating MS has never been subjected to a well-controlled clinical trial.

The supposed large clinical effect of the Swank low fat diet led to our hypothesis that a very-low-fat, plant-based diet might have a large effect on MRI activity. We conducted a pilot study to explore the tolerability and potential benefits of a very-low saturated fat, plant-based diet followed for 12 months by people with relapsing-remitting MS (RRMS) with the primary endpoint being brain MRI disease activity.

 

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