Mom's Story

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Study Strengthens Link Between Low Vitamin D Levels and Risk of MS

SUMMARY

  • A study based on stored blood samples of 800,000 pregnant Finnish women found that vitamin D levels might predict who is at risk for later developing MS.
  • Vitamin D blood levels of 1,092 women later diagnosed with MS were compared to those of 2,123 women around the same age and region who did not develop the disease.
  • Women who developed MS later had average D levels lower than the women who didn’t.
  • More research is needed on how to best supplement vitamin D and to know whether and who it might help. Read more more about Vitamin D and MS.
  • The study was published on September 13, 2017 in Neurology.

DETAILS
Background: Researchers believe that several genetic and environmental factors influence whether a person will get MS. These factors may also impact the severity of the disease. Scientists are eager to find risk factors for MS that can be modified to possibly prevent MS and reduce disease activity. Research is increasingly pointing to reduced levels of vitamin D in the blood as a risk factor for developing MS, and studies are underway to determine if vitamin D levels influence MS disease activity.

This Study: This study — the largest such study to date – took advantage of a unique resource: stored blood samples from 800,000 Finnish women who had undergone routine prenatal testing during pregnancy. The study was designed to determine whether and to what extent vitamin D deficiency is associated with future risk of developing MS. The team identified 1,092 of the women who were later diagnosed with MS. The researchers compared their vitamin D levels to those of 2,123 women who were about the same age and lived in the same area but did not develop MS. Of those women whose medical records were available for examination, an average of 9.5 years had lapsed between the time of the first blood sample and the date of an MS diagnosis. For this study, classifications of blood levels of vitamin D (25-hydroxyvitamin D) included “deficient” (less than 30 nmol/L) and “adequate” (greater than or equal to 50 nmol/L).

Results: The team found that overall as vitamin D levels increased, the risk of later developing MS decreased. Women with the greatest deficiency in vitamin D had a twofold increase in the risk of developing MS, and those with the highest vitamin D levels had the lowest risk of a later MS diagnosis. Most of the women in the study were considered to have deficient or insufficient levels of vitamin D. Of the women who developed MS, 58 percent had deficient levels of vitamin D, compared to 52 percent of the women who did not develop the disease.

The researchers conclude that the results directly support vitamin D deficiency as a risk factor for MS and that correcting this among reproductive age women may reduce their future risk of developing MS. In addition, a previous study of this same group of women found that maternal vitamin D deficiency during pregnancy doubled the risk of MS in their offspring, and a Danish study found that low vitamin D levels in infants was associated with an increased MS risk in adulthood, suggesting that improving a woman’s vitamin D levels during pregnancy may also reduce the risk of MS in her children.

The study, by a team including Drs. Kassandra Munger and Alberto Ascherio (Harvard T. H. Chan School of Public Health in Boston), was published on September 13, 2017 in Neurology.

Comment: This largest study of its kind to date adds to growing evidence that low levels of vitamin D increase the likelihood of developing MS. Since this study included only women, who were mostly white, the results may not apply to men or to other racial groups. It also did not account for other potential risk factors that may have played a role.

An editorial in the same issue of Neurology by Drs. Ruth Ann Marrie Christopher Beck addresses the question of whether there is enough evidence now to make sweeping recommendations on vitamin D supplementation. They note, “Vitamin D supplementation is a simple intervention that would be highly cost-effective even if it prevents only a proportion of MS cases…,” concluding, “It is time to take an active approach to preventing MS, at a minimum targeting those individuals with an elevated risk of MS, including smokers, the obese, and those with a family history of MS.”  Read more more about Vitamin D and MS

 

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World’s Largest MS Research Conference Highlights Advances in Progressive MS, Gut Microbiome, Managing Symptoms, and New Approaches to Restoring Function

Results from clinical trials, including new approaches to treating progressive MS, lifestyle and wellness research and myelin repair strategies were among more than 2,000 presentations made at the European Committee for Treatment and Research in MS (ECTRIMS) meeting held in London, England in September.
The world’s largest gathering of MS researchers convened more than 9,000 scientists and clinicians and industry representatives from across the globe, including many National MS Society-funded researchers, meeting and presenting on cutting-edge MS research progress. In addition, the European Rehabilitation in MS network met jointly with ECTRIMS this year.

During the conference, the International Progressive MS Alliance announced new investments of over $14 million US dollars to support three Collaborative Network Awards. These international teams were selected to accelerate the pace of research in key areas to speed new therapies for progressive MS.

Below are highlights of presentations focused on stopping MS, restoring function, and ending MS forever. In most cases, studies presented are considered preliminary. Many will be analyzed more thoroughly, and likely published in peer-reviewed journals.

STOPPING MS

Many presentations showed continued benefits of available therapies and longer-term safety information, as well as more evidence that early and ongoing treatment with a disease-modifying therapy has long-term benefits for controlling disease activity, delaying accumulation of disability, and protecting quality of life.

Siponimod in secondary progressive MS: More details were presented from a 60-month, phase 3 clinical trial of the experimental oral therapy siponimod (Novartis Pharmaceuticals AG) involving 1,651 people with secondary progressive MS. The trial met its primary endpoint, with those on active treatment showing a modest 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 MRI-detected lesion volume. The medication showed a similar safety profile to others that work by preventing white blood cells from entering the central nervous system. (Abstract #250)

More details from trial of lipoic acid in secondary progressive MS: Dr. Rebecca Spain and colleagues (Oregon Health & Science University) presented results from a small, controlled clinical trial on the oral anti-oxidant supplement called lipoic acid in people with secondary progressive MS. The lipoic acid group had 66% less brain tissue shrinkage, or atrophy, than the group taking inactive placebo pills. This pilot study suggests potential benefits if they hold up in a larger trial. (Abstract #222)

New results on gut bacteria: Efforts are advancing to pinpoint bacteria in the gut that may drive inflammatory immune system activity in MS and others that can suppress it, which may open the door to novel probiotic or other therapeutic approaches to treating MS.

  • Drs. Yan Wang, Lloyd Kasper and colleagues (Dartmouth Medical School and Eastern Washington University) reported that treating mice with the gut-related molecule called polysaccharide A (PSA) expanded a type of immune cells called “Regulatory B cells” (Bregs) which promote an immune response that prevents mice from getting MS-like disease. (Abstract #181) Members of this team also reported that PSA had positive effects in mice with progressive MS-like disease. (Abstract #P465)
  • Dr. Sergio Baranzini (University of California, San Francisco) and other collaborators in the National MS Society-supported MS Microbiome Consortium are analyzing gut bacteria to unearth clues about MS susceptibility and progression. They analyzed bacteria in stool samples from 64 people with MS who had received treatment for MS, and 68 people without MS. Certain bacteria were increased in people with MS, and those bacteria increased immune cells (T helper 1 cells) that are major players in MS immune attacks. Another type of bacteria that could suppress the immune attack was reduced. (Abstract #179)

Disappointing results for nerve-protection approaches: A small two-year clinical trial of fluoxetine (same compound as the anti-depressant Prozac) did not meet its goal of improving walking speed in people with progressive MS. The multi-center team from Belgium is still analyzing other results, such as changes in MRI and cognition. (Abstract #253) Likewise, a trial conducted at the University of Oxford tested the ability of amiloride to protect against nerve damage in people with acute optic neuritis (often an early sign of MS) failed to show any neuroprotective benefit. (Abstract #102) Additional trials of neuroprotective approaches to MS are ongoing.

Vitamin D deficiency and smoking linked to progression: Dr. Maria Isabel Zuluaga and team (Vall d’Hebron University, Barcelona) explored the independent impacts of smoking and vitamin D deficiency in a large group of people followed over time. They found that those with severe vitamin D deficiency (defined as blood levels at less than 8 ng/ml) showed an increased risk for MS disability, and active smokers also had an increased risk for disability progression. (Abstract #252) Graduate student Ms. Eva Rosa Petersen (Danish MS Center, Copenhagen) also found that smoking intensity was linked with higher frequency of relapses among people taking interferon beta. Smoking one pack of cigarettes per day increased relapse rates by 25%. (Abstract #178)

Vitamin D added to Rebif: A large international trial did not show a statistical difference between treatment groups after adding vitamin D (14,000 IU [350 µg] vitamin D3 daily) or placebo to Rebif therapy in relapsing MS, in terms of the percent of participants who were free from disease activity after 48 weeks. Dr. Raymond Hupperts (Orbis Medical Centre, Sittard-Geleen, The Netherlands), who presented results, noted that both groups were stable, which likely contributed to the inconclusive results. (Abstract #166)

Biomarkers under development: Teams are making headway toward having a simple test that can predict a person’s disease course, progression and response to therapy. Dr. Bibiana Bielekova (National Institute of Neurological Diseases and Stroke) and team examined proteins in the spinal fluid of people with neurological diseases, including all types of MS, and identified a “signature” of markers that distinguished MS from other diseases, and also differentiated relapsing MS from progressive MS. (Abstract #219). Other investigators also reported progress in this area, including advances using “neurofilament light chain” as a biomarker. (Such as Abstracts #183, #249) These early results need further development but indicate that  sensitive biomarkers for predicting disease course and response to therapy may become useful tools for the clinical management of MS.

RESTORING FUNCTION – WELLNESS, LIFESTYLE, SYMPTOMS

Home-based rehabilitation can work: With funding from the National MS Society, Dr. Gabriel Pardo (Oklahoma Medical Research Foundation) and colleagues compared the benefits of three approaches to rehabilitation for gait and balance in a small study: unsupervised home-based exercise 5 times/week; home-based exercise supervised remotely by a physical therapist 2-3 times per week via audio and visual conferencing; and home-based exercise plus in-person physical therapy 2-3 times/week. They found that all participants improved, and that the telerehabilitation program worked as well as the onsite program to improve gait and balance. Further research in larger trials could make telerehabilitation a cost-effective and more accessible alternative for people with MS. (Abstract #120)

Tackling fatigue: Dr. Vincent de Groot (VU University Medical Center, Amsterdam) reported results from three clinical trials testing different strategies over 16 weeks to lessen fatigue, in 90 people with MS: aerobic training, cognitive behavioral therapy, and energy conservation management. Only cognitive behavioral therapy effectively reduced severe fatigue in this short-term study. This is a commonly available type of psychotherapy. (Abstract #142) Read more about managing fatigue

Pain more common than previously reported: Dr. Carolyn Young (University of Liverpool) and colleagues found that nearly 66% of over 700 people with MS reported nerve pain. Higher levels were found in those who had MS for a longer time, had more severe disability, or were not working. (Abstract #P337Read more about addressing pain in MS

New trial confirms Ampyra (fampridine) benefits: Dr. Jeremy Hobart (Plymouth Hospitals NHS Trust) presented results from a large clinical trial of fampridine, a twice-a-day oral therapy that was previously approved for its ability to improve walking.. This trial wanted to show evidence that its benefits include meaningful functional improvements for people. The results over 6 months showed that 43% of those on active therapy had significantly better self-reported walking ability, mobility, and balance than those on placebo, with no new safety issues reported. (Abstract #254)

Cognitive rehabilitation enhances brain connections: Several studies showed that rehabilitation to improve cognition goes hand-in-hand with changes in brain connectivity (how areas of the brain interact). While many of these treatments are still experimental, some are available from rehabilitation specialists such as speech pathologists or neuropsychologists. Discuss options with your MS doctor:

  • Dr. Brian Sandroff (Kessler Foundation, West Orange, NJ) and colleagues showed that treadmill training improved information processing speed and brain connectivity in a small pilot study funded by the Society. (Abstract #P796)
  • Dr. Pietro Iaffaldano (University of Bari, Italy) and colleagues showed that a home-based computerized training program that targeted specific cognitive issues improved overall cognitive function significantly more than a non-specific program. Also, those who had less function in certain brain areas showed greater improvement after cognitive training. (Abstract #145)
  • Oiane Rilo (University of Deusto, Bilbao, Spain) and colleagues showed that a three-month, group-based cognitive rehabilitation program improved working memory, information processing speed, verbal memory and executive function (which is important in problem solving and planning), and altered brain connectivity. (Abstract #144)

Emerging treatment for muscle spasticity: Dr. Daniel Kantor (Kantor Neurology, Ponte Vedra Beach, FL) and colleagues report that in a trial of 354 people with relapsing-remitting or secondary progressive MS, Arbaclofen Extended Release Tablets (Osmotica Pharmaceuticals) significantly reduced spasticity compared to baclofen. The extended-release tablets caused significantly less sleepiness, drowsiness and dizziness than baclofen. (Abstract #128) The company reports that it has filed for FDA approval of Arbaclofen.

RESTORING FUNCTION – NERVOUS SYSTEM REPAIR

More Anti-LINGO Results: In June 2016 Biogen announced that its phase 2 clinical trial of anti-LINGO (proposed name opicinumab), an approach to repair myelin, did not meet its primary endpoint of improvement in physical function, cognitive function, or disability. The trial involved 418 people with relapsing MS who were taking interferon beta-1a (Avonex) plus one of several doses of intravenous opicinumab or placebo for 72 weeks. Dr. Diego Cadavid from the company described ongoing evaluations from the extensive testing and monitoring during the trial, which are helping to pinpoint the patient population, dosage and outcome measures that would inform the design of any future trials of anti-LINGO.  (Abstract #192)

Myelin repair in pediatric and adult MS: Dr. Sabine Pfeifenbring (University of Göttingen, Germany) and an international team analyzed brain biopsies from children who had been diagnosed with MS and compared the extent of damage and natural myelin repair against those of adults with MS. They found that children showed less damage to myelin-making cells and more evidence of myelin repair than adults. However, some myelin repair was found to occur at virtually all ages in MS. (Abstract #194)

Exercise enhances myelin repair in mice: To investigate some reasons why exercise promotes benefits in people with MS, Drs. S. Jensen and Wee Yong (University of Calgary) did a study where mice with myelin damage in their spinal cords used running wheels soon after the injury. They reported finding more evidence of generation of myelin-making cells and myelin repair in the active mice than those that did not use the running wheels after injury. (Abstract: #P1210)

Emerging approaches to protection and repair:  Dr. Martin Sanders (Io therapeutics) presented results from mice suggesting that the compound IRX4204 promotes repair of damaged myelin in mice. He noted that previous studies suggested that IRX4204 also showed signs of reducing immune attacks and protecting against nerve loss. This work was supported in part by a National MS Society’s Fast Forward investment. (Abstract #193)

Drs. Sarah Starossom, Samia Khoury and team (Brigham and Women’s Hospital, Boston) reported on studies of Chi3l3, a naturally occurring molecule in the brain that can stimulate the transformation of resident stem cells into myelin-making cells. The team noted that it plays an important role in recovery from the MS-like disease in mice, and may have potential for development as a new treatment approach in MS. (Abstract #195)

Writing Mom’s Story

I began writing the story in late 2007. Actually, I began the story in February 1978. Immediately after getting out of bed that February morning, I couldn’t stand. The room was whirling, my stomach was churning. I sat on the edge of t he bed until my head cleared a little and I could stand. I tried to dress, but wasn’t able to bend down without the room spinning again and the nausea returning. I made a doctor’s appointment. He couldn’t find anything and treated me with Dramamine for a mild middle ear inflammation. It cleared after about a week and I put the occurrence in the back of my mind. In August of the same year, I awoke one morning with a gray spot in the vision of my left eye. It enlarged over the morning. By afternoon, my vision in my left eye was limited to the extreme outer edges. Being Saturday, I went to the Emergency Room, convinced I was going blind. An Ophthalmologist happened to be on duty. He diagnosed the problem immediately as optic neuritis and prescribed prednisone. That cleared in about eight weeks.
Fast forward to 1989. I had been a “normal volunteer” at the National Institutes of Health for several years. I was asked if I would volunteer for an MRI. They said it’s easy if you’re not claustrophobic, no needles, only some noise. I said I would be glad to do it. They were right, lots of noise but no other discomforts. About a week later, a physician called to tell me that they found something strange on my brain. I went back to the physician and came away with a definite diagnosis of multiple sclerosis (MS). I launched a search for information, this being pre-internet, I went to libraries and contacted the National Multiple Sclerosis Society (www.nmss.org ).
By June of 2006 I had retired on disability from my position as a Science Librarian and worked from home as an editor and writer. I attended a meeting of the Outdoor Writers Association of America (www.owaa.org ). I was interested in writing for children by this time and I attended a session given by the renowned children’s author, Kathleen Kudlinski (www.kathleenkudlinski.com ). Her one piece of advice (among others) that I took away from her presentation was: “Write what you know.”
In October 2007, after spending over a year researching and learning about writing for children, I asked myself, “What do I know?” It came to me quickly, I know about MS. I have been interested in health issues and have read quite extensively, especially about plagues and infectious diseases. But also about MS, I have an extensive library about the disease and I have reviewed books on the subject for Library Journal.

Now in it’s second edition.

Study Suggests Adolescent Obesity and Genetic Factors Interact to Increase MS Risk

In a study comprising two large populations of people with MS and controls without MS, adolescent obesity was confirmed to increase a person’s risk for later developing multiple sclerosis, and this risk increased substantially in those with specific risk genes that control the immune system (known as HLA). Anna Karin Hedström, MD (Karolinska Institutet, Stockholm, Sweden) and colleagues in Sweden and California report their findings in Neurology (2014;82:1–8). More research is needed to confirm these results and to determine other risk factors that may help determine who is susceptible to MS and who is not.

Background: While MS is not contagious or directly inherited, epidemiologists—the scientists who study patterns of disease—have identified factors in the distribution of MS around the world that may eventually help determine what causes or triggers the disease. These factors include gender, genetics, age, geography, and ethnic background. The MS susceptibility genes identified to date are generally not clinically useful for providing genetic counseling to individuals regarding who may develop MS.

Because the prevalence of obesity has increased dramatically in the past several decades, and obesity is associated with an increase in immune system activity, researchers are seeking to determine if there was any association between obesity and the risk for developing MS.

Researchers recently reported that being overweight or obese was associated with an increased risk of developing MS or clinically isolated syndrome (CIS, a first clinical episode suggestive of MS, indicating increased MS risk) in girls, in a study that compared 75 children or teens with MS or CIS with the health records of more than 900,000 healthy children or teens (Neurology February 5, 2013 80:548-552).

The Study: Investigators used data from two studies on environmental and genetic risk factors, analyzing two populations: one that had 1,510 cases of MS and 2,017 controls without MS and another that comprised 937 cases and 609 controls. They obtained information on two genes previously associated with MS risk (the presence of “HLADRB1*15,” thought to increase MS risk, and absence of “HLA-A*02,” thought to be protective against MS), body mass index at age 20, and development of MS.

In both study populations, adolescent obesity was associated with increased risk of MS, as was the presence of HLADRB1*15or the absence of HLA-A*02. Participants who showed both adolescent obesity and either of the genetic risk factors had nearly an eight-fold increased risk of developing MS compared to those who were not obese in adolescence and who did not have any of the genetic risk factors.  However those who reported adolescent obesity and both of the genetic risk factors had a 16-fold or 14-fold increase in risk of MS.

Conclusions: This study adds to the growing body of evidence that adolescent obesity is a risk factor for developing MS. The authors note that “biologic explanations are far from clear,” but they suggest that immune mechanisms associated with obesity may be active in driving the disease in people who are genetically susceptible. Additional research is needed to understand this association. It is important to note that not everyone who is obese during adolescence will develop MS, and also that many people develop MS without having been obese during adolescence.

“We should be concerned about these findings,” cautions Ruth Ann Marrie, MD, PhD (University of Manitoba, Winnipeg, Canada) and Christopher A. Beck, PhD (University of Rochester Medical Center, NY) in an accompanying editorial. “It is time to begin developing a targeted approach to prevent MS by improving common health behaviors, including body weight and smoking.”

About Multiple Sclerosis

Multiple sclerosis, an unpredictable, often disabling disease of the central nervous system, interrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are moving us closer to a world free of MS. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.

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