New Lab Studies Add Evidence That High Salt Diets Increase Inflammation and May Have Implications for MS

Summary

• The results from two recently published laboratory studies suggest that high levels of salt shift the balance of the immune system toward inflammation, and that salt alters the function of several types of immune cells pertinent to MS.
• These two studies, which were both published in the Journal of Clinical Investigation, were led by Dr. David Hafler (Yale University) and Dr. Dominik Müller (Max-Delbruck Center, Berlin, Germany).
• Dr. Hafler is funded by the National MS Society to study the impact of high salt on the immune system, and the Yale team is also conducting a pilot clinical trial to explore the impact of high- and low-salt diets on MS disease activity.

Background: Eating high levels of salt, which is part of the typical Western diet, has been linked to heart disease, chronic inflammation, and cancer. Recent lab reports have also suggested that dietary salt can speed the development of the immune attack in an MS-like disease in mice, and that the mouse disease responds differently to salt depending on the gender and genetic makeup of the mice. One small study in people found a possible link between dietary salt levels and relapses in people with MS, but this study suggested a link, which is not the same as establishing an actual cause. So far, laboratory findings related to the effects of salt have been stronger than the few studies that have been reported in people. Understanding whether high dietary salt is a risk factor for developing MS or for worsening disease activity is an active area of research.

The Studies: Two studies recently published in the Journal of Clinical Investigation suggest that high dietary salt affects two types of immune cells in a way that increases inflammation, a state that is generally considered harmful in MS. A study by National MS Society-supported researchers at Yale University and Harvard Medical School led by David Hafler, MD, investigated the effects of high salt on regulatory immune cells called “Tregs.” Tregs normally suppress immune responses by other immune cells, but in people with MS Tregs have been shown to be less able to perform this helpful function to turn off attacks. The team showed in mice and in cells in lab dishes that high salt blocks the ability of Tregs to suppress potentially harmful immune cells, and shifts Tregs toward activity that increases inflammation.

The other study, by an international team led by Dominik N. Müller at the Max-Delbruck Center in Berlin, Germany, investigated immune cells called “macrophages.” This study showed that high salt blocks the activation of a subset of macrophages, reducing their ability to suppress inflammatory cells and creating an imbalance in the immune system. In mouse models, high salt diets also delayed wound healing.

Comment: Taken together, these laboratory studies add new evidence that high levels of dietary salt may increase inflammation and autoimmunity, and decrease the ability of regulatory cells and processes to limit harmful immune cell activity. More studies are needed to determine the possible role of a high-salt diet in the risk of developing MS and whether reducing salt intake may be helpful for reducing disease activity in people with MS. Dr. Hafler is funded by the National MS Society to study the impact of high salt on the immune system, and the Yale team is also conducting a pilot clinical trial to explore the impact of high- and low-salt diets on MS disease activity.

Read more about dietary factors that may play a role in MS
Read more about research on the immune system in MS

Researchers seek volunteers for self-compassion survey

Oregon State University researchers are seeking participants for an online survey to investigate the relationship of self-compassion on resilience, physical activity, and quality of life for individuals with MS.

Subjects between the ages of 18 and 65 who can communicate in English and have a medical diagnosis of MS are eligible to participate in this study. The survey takes 20 to 30 minutes to complete. Participation in the survey is voluntary. Personal identification information will be removed from the survey data.

Survey answers will help improve understanding of the process of self-compassion and physical activity on improving health-related quality of life for individuals with MS. Results from this study will also help researchers develop effective health interventions to improve wellness and quality of life for people with MS.

To complete the survey, visit http://oregonstate.qualtrics.com/SE/?SID=SV_8ktgzQ9Jki71UEt

If you are interested or have any questions, contact the research team at nerym@onid.oregonstate.edu.

Mom's Story, a Child Learns about MS is available in more formats

Mom's Story can be found on the following sales channels:
Apple -
Kobo -
Oyster -.
Page Foundry -.
Scribd -
Tolino -
Also available on Kindle, Nook,
Available as .Mobi and .epub files from mjnickum@saguarobooks.com

MS Trial Alert: Investigators Nationwide Recruiting People with MS for Phase I Study to Determine Safety of Experimental Antibody in Treating Relapse

Summary: Investigators nationwide are recruiting 30 people with MS for a phase I study to determine the safety and tolerability of rHIgM22, an experimental antibody. Participants may remain on their current therapy throughout the study. The study is enrolling participants experiencing a clinical acute relapse (new or worsening neurological symptoms attributable to MS preceded by a stable or improving neurological state of at least 30 days) and with at least one new, active lesion (damaged area) on MRI scans. The study is funded by Acorda Therapeutics, Inc.
Rationale: Although the body repairs some damage to nerve-insulating myelin that occurs in MS, this repair is insufficient. One strategy under study is to stimulate the body’s own internal repair capabilities. With funding from the Hilton Foundation, NIH, the National MS Society and others, Moses Rodriguez, MD, and colleagues (Mayo Clinic Foundation) identified a human antibody – rHIgM22 – that targets and attaches to myelin-making cells. When given to mice with an experimental MS-like disease, rHIgM22 promotes myelin repair. This antibody was well tolerated in another phase I study (trial NCT01803867, as listed on clinicaltrials.gov) in 55 people with all types of MS. (Abstract #P4.339, Annual Meeting of the American Academy of Neurology 2015)
Eligibility and Details: Men and women between the ages of 18 and 70 with a diagnosis of MS are eligible. The study is enrolling participants with a clinical acute relapse; an MRI will be performed to confirm that there is an active lesion (damaged area). There are detailed exclusion criteria related to laboratory, cardiac, immune and other factors. For more information on these criteria, please use the contact information below.
Participants will remain on their current therapy throughout the study. Upon entering the study with an acute relapse, subjects will receive high-dose oral steroids for five days, a standard treatment for an acute relapse. Following completion of the oral steroids for the acute relapse the subjects will receive either a single dose of rHIgM22 or placebo.
Investigators are testing 2 dose levels. For each dose, 10 participants are being randomly assigned to receive active treatment (rHIgM22) and 5 are being randomly assigned to receive inactive placebo, both via a single intravenous infusion. Blood samples will be collected from participants before and at specified times for up to 48 hours after dosing, so participants must agree to remain in the hospital for that time. Participants are being followed for 180 days after dosing, which includes return visits to the clinic and MRI scans.
The primary outcome of the study is to determine the safety and tolerability of rHIgM22 in people with MS. Adverse events are being monitored throughout the study. The investigators will also evaluate how this experimental treatment is absorbed in the body, and how the immune and nervous systems react to it. Phase I studies are the first of three stages of clinical trials that determine whether an exploratory treatment is safe and beneficial.
Contact: To learn more about the enrollment criteria for this study, and to find out if you are eligible to participate, please contact Kevin Cronin, Manager Corporate Communications, kcronin@acorda.com, 914-326-5279, or visit the trial’s listing on clinicaltrials.gov to find the site nearest you.
Sites are recruiting in the following cities:
Aurora, CO
Centennial, CO (Denver metro-area)
Dallas, TX
Indianapolis, IN
Long Beach, CA
Rochester, NY
Sacramento, CA
Saint Louis, MO
San Francisco, CA
Seattle, WA
Stanford, CA
Teaneck, NJ (NY metro area)
Download a brochure that discusses issues to think about when considering enrolling in an MS clinical trial (PDF).
 

Study Shows MS Progresses Faster in Those Who Continue to Smoke

Summary

• A new study involving people with MS who smoked cigarettes suggests that those who continued to smoke after receiving an MS diagnosis were quicker to reach the secondary-progressive phase of MS than those who quit after diagnosis.
• Those who continued to smoke converted to secondary-progressive MS at a median age of 48, while those who quit smoking within the year after MS diagnosis progressed at a median age of 56.
• This adds to evidence that smoking may speed progression of MS, and offers new evidence that quitting smoking after MS diagnosis may slow progression.
• The team (Ryan Ramanujam, PhD, Jan Hillert, MD, PhD, and colleagues at Karolinska University Hospital Solna, Stockholm, Sweden) has published results in JAMA Neurology (Published online September 8, 2015). The full paper is available free of charge.

Background: In most people, MS begins with a relapsing-remitting course with defined attacks of worsening neurologic function, followed by periods of partial or complete recovery. Most people eventually transition to secondary-progressive MS, where the disease begins to progress or worsen more steadily, with or without relapses. The factors that determine if or when a person may transition to secondary-progressive MS are not fully understood. Some studies have found that smoking is related to disease progression, and that MS disability progresses more quickly in smokers, but the impact of quitting after diagnosis had not been thoroughly determined.
The Study: Investigators identified 728 people with MS who smoked at the time of MS diagnosis and were enrolled in the large Genes and Environment in MS Study in Sweden. Of these, 332 were classified as “continuers” who smoked at least one cigarette per day continuously from the year after diagnosis and 118 were considered “quitters,” who had stopped smoking within the year after diagnosis. A group of 278 were “intermittent smokers” but were not included in the final evaluation.
The main focus of the study was to determine how smoking was related to conversion to secondary-progressive MS, which occurred in 216 people. The researchers found that each year of smoking after diagnosis accelerated the time to conversion to secondary-progressive MS by 4.7%. Continuers progressed to secondary-progressive MS faster (at a median age of 48) compared with quitters (age 56).
Results were published in JAMA Neurology (Published online September 08, 2015). The full paper is available free of charge.
Comment: This is an important study that adds to evidence that smoking speeds progression of MS, and offers new evidence that quitting smoking after MS diagnosis may slow progression. In an accompanying editorial, Drs. Myla D. Goldman (University of Virginia, Charlottesville) and Olaf Stüve (University of Texas Southwestern Medical Center at Dallas) comment that this may be the first evidence that quitting smoking can delay conversion to secondary-progressive MS. “Therefore, even after MS diagnosis, smoking is a risk factor worth modifying,” they write.
The National Institutes of Health provides resources to help quit smoking: visit smokefree.gov or call 1-800-QUITNOW (1-800-784-8669).

Out for a time...

For medical reasons, I will be unavailable until mid October.

Case of PML Reported in Person Taking Tecfidera®

In December 2014, important label changes were made to the prescribing information for Tecfidera® (dimethyl fumarate, Biogen Idec) including information regarding an individual who developed PML. Most recently, Biogen has confirmed report of a second case of PML (progressive multifocal leukoencephalopathy, a viral infection of the brain that often leads to death or severe disability) that occurred in a person taking Tecfidera. According to the company, the 64-year-old patient has primary progressive MS and experienced severe and prolonged lymphopenia (decreased white blood cells) during treatment with Tecfidera. Severe and prolonged lymphopenia is a known risk factor for PML and Consideration should be given to interrupting treatment if lymphocyte counts are low for more than six months.  The patient is stable and is not hospitalized. Biogen has reported the case to the U.S. Food and Drug Administration (FDA).

PML is caused by the re-activation of a virus called the JC (John Cunningham) virus, a common virus to which many people have been exposed. PML has emerged in people using other medications, including the MS treatment Tysabri® (natalizumab, Biogen), and the MS treatment Gilenya® (fingolimod, Novartis AG).

It is not possible at this point to determine a person’s risk for developing PML because there have been so few cases in people taking Tecfidera. There have been two reported cases of PML in people with MS among the more than 155,000 individuals who have been treated with Tecfidera to date.

The symptoms of PML are diverse and can be similar to MS symptoms. For this reason, individuals should be alert to any new or worsening symptoms and report them promptly to their MS healthcare provider.  Learn more about the risk factors and symptoms of PML from the web site of The PML Consortium. Individuals who have concerns about this report should discuss it with their MS healthcare providers.

If and when the FDA or Biogen provide additional information or recommendations for people taking Tecfidera or other MS medications, the National MS Society will share it as soon as possible.