In a new study from Germany of 453 children and teens with MS, compared with more than 14,000 children without MS, those who were overweight or obese had twice the risk of developing MS, compared with non-overweight children.
They also had significantly more relapses on treatment with first-line treatments, and increased use of second-line treatment. Otherwise, there was no association found between obesity and disease activity, imaging scans, EDSS progression, or other measures.
These findings need to be confirmed with further study. 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.
The team (Brenda Huppke, MD, Peter Huppke, MD, and colleagues at University Medical Center Göttingen, Germany) published their findings in JAMA Neurology (posted online July 15, 2019)
Background: Several risk factors, including genes, exposure to infections, and environmental factors, have been identified as increasing a person’s susceptibility to developing multiple sclerosis. In addition, there is a growing body of evidence that childhood/adolescent obesity can increase the risk of developing MS. In one study, 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.
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.
The Study: The researchers reviewed the medical records of 453 children and adolescents with relapsing-remitting MS. They looked at disease activity captured on imaging scans; treatment information, and EDSS scores measuring levels of physical disability. They also compared body mass index with information obtained on 14,747 children/adolescents in a Germany-wide child health survey.
Results: The team found that both boys and girls who were overweight or obese had twice the risk of developing MS, compared with non-overweight children or adolescents. Comparing responses to treatment with interferon beta or glatiramer acetate, the team reported that obese children had significantly more relapses on treatment, and were more likely to have switched to second-line treatment. Otherwise, there was no association found between obesity and disease activity, imaging scans, EDSS progression, or other measures.
The team (Brenda Huppke, MD, Peter Huppke, MD, and colleagues at University Medical Center Göttingen, Germany) published their findings in JAMA Neurology (posted online July 15, 2019)
Conclusions: This study provides strong support for a link between obesity and development of MS in both boys and girls. It also indicates a significantly worse response to first-line MS treatments and a greater likelihood of switching to second-line treatments among obese children. The authors suggest that obesity may affect pharmacokinetics – how a drug moves into, through, and out of the body. Further research is necessary to confirm these findings, and to understand the mechanism.
There is exciting and innovative research and progress occurring related to the potential of many types of stem cells for slowing MS disease activity and for repairing damage to the nervous system. In light of the urgent need for more effective treatments for MS, particularly for those with more progressive forms of the disease, we believe that the potential of all types of cell therapies must be explored.
Stem cell therapy is any treatment that uses or targets stem cells, which are the types of cells that differentiate into many different specialized cells in our bodies. Stem cells are found in both embryos and adults.
Many types of stem cells are being explored for their potential benefits for treating multiple sclerosis. Only when the results of these and subsequent clinical trials are available will it be possible to determine what the optimal cells, delivery methods, safety and actual effectiveness of these current experimental therapies might be for people with MS.
Although cell based therapy has generated a great deal of interest and holds promise, the field is in its infancy and much more research is needed before cell based therapies become a MS treatment option.
Different Types of Stem Cells
www.nmss.org The National Multiple Sclerosis Society
Multiple Sclerosis (MS) is a disease that impacts the body’s central nervous system (CNS) including the brain, optic nerves, and spinal cord. MS consists of an abnormal response of the body’s immune system. From here, the immune system targets myelin (a substance that surrounds and insulates the body’s nerves), and myelin gets damaged, which then produces scars (sclerosis). These scars are believed to be the cause of the painful symptoms MS patients experience.
Although MS causes various painful symptoms, over 85 percent of MS patients experience spasticity. Fortunately, though, based on the studies have been conducted on cannabis and MS so far, most indicate that cannabinoids are associated with self-reported spasticity improvements. It has also been found that CBD contains anti-spasm properties. Additionally, the American Academy of Neurology has expressed that cannabis is effective for the treatment of pain and spasticity. Then, one Israel study discovered that cannabis can safely alleviate pain in older MS patients and those with other chronic conditions, such as Crohn’s Disease.
Currently, 20-60 percent of MS patients consume cannabis, and many use topical cannabis products as their primary delivery method. To help treat muscle spasms and pain, it’s common for MS patients to use cannabis topically, so they can apply the medicine onto specific areas of their body. To achieve localized and rapid relief though, it’s recommended to use topical products with one example being CanniMed’s products, from which numerous Canadian MS patients have benefited.
A new study funded by the National MS Society has confirmed that nearly one million people are living with MS in the United States, more than twice the original estimate from a previous study. This breakthrough is a pivotal moment in the MS movement as a scientifically sound measure of prevalence helps us better understand the disease and its impact. With twice as many people living with MS, solutions for MS are now twice as important.
In addition to the main paper outlining these results, two companion papers providing background information on prevalence in the U.S. and reviewing the study methods were also published in the February 15, 2019, online issue of Neurology®, the medical journal of the American Academy of Neurology.
Q: What is prevalence and how is it different from incidence?
A: Prevalence is the number of people living with a disease. Incidence is the number of people newly diagnosed with a disease within a given period of time.
Q: How many people are living with MS in the U.S. according to the new prevalence estimate?
A: Nearly 1 million people (913,925)
Q: How is the new estimate different than numbers used before?
A: More than twice as many people are living with MS than was previously thought.
Q: Where did the earlier MS prevalence number of 400,000 come from?
A: The previous figure of 400,000 was an estimate calculated from population growth since the national study of MS prevalence that was published in 1981.
Q: Why is this information important? And what does it mean for people affected by MS and the work of the National MS Society?
A: Having this scientifically sound prevalence estimate will facilitate a better understanding of the needs of people with MS and the economic burdens imposed by the disease on families and society. It will be a starting point for researchers to understand if MS is increasing, or if there are MS geographic clusters that hold clues to factors that trigger MS. These data will also help ensure that the National MS Society is able to connect to and support all people affected by MS.
Q: Does this mean more people are getting MS than before?
A. We don’t know. Since solid information on the number of people being diagnosed with MS has not been available, it has been difficult to tell whether more people are getting MS or if the total number is just a reflection of overall population growth, better diagnostic procedures, the availability of disease modifying drugs, or other changes in the MS landscape. Going forward, this should become easier. Outside of the U.S., some studies have reported increases in the incidence of MS. More work is needed to understand all the factors that led to this increase.
Q: What was the process to reach this new number and why has it taken so long to get an updated prevalence number of people living with MS in the U.S.?
A: After an examination of what it would take to identify a scientifically sound estimate, the Society funded the work and established a work group of experts across the fields of epidemiology, statistics and health care. This group labored for nearly four years to develop and implement a plan for estimating prevalence as rigorously as possible given the sources of information available. They obtained the proper mix of administrative datasets, developed and validated a formula to identify people with MS then applied it, and the findings were published in a peer-reviewed journal.
Q: Will this change the global number?
A: Yes, this will change the global number (which is most recently estimated at 2.3 million). The global number is calculated through input from MS societies across the globe to the MS International Federation. The MS International Federation is planning to do an update of the “MS Atlas” and when complete, the global number is likely to increase not just from the new U.S. estimate but from other nations as well.
Q: How confident are we in this number?
A: A team of experts led a thorough study based on a sound, scientific process and followed the peer-review process to affirm these results. We have trust and confidence in the approach and methodology that produced these results. In addition, the figures for the US are as high or higher than figures found in other countries using a variety of different methods to calculate the number.
Q: Will this new prevalence estimate help us get to a cure for MS faster?
A: Research breakthroughs related to what causes MS and how to cure it are happening at a faster pace than ever before. Having sound information on how many people are living with MS and who gets MS is an important pathway to a cure.
Q: When and how will the prevalence number be updated again?
A: The National Neurological Conditions Surveillance System, which was authorized in 2016 through the 21st Century Cures Act, has been funded and will be able to update prevalence estimates on a regular basis. This is a culmination of more than a decade of work by MS activists and others across the neurologic community. This system will provide important demographic data to help researchers move more quickly toward cures for the millions of people who live with diseases like MS and Parkinson’s.
Q: Why do we only have an estimate of the number of people with MS, versus knowing the exact figure?
A: Unlike for certain infectious disorders, there is no requirement for healthcare providers to report to health authorities when a person is diagnosed with MS. Although a nearly exact count could be made by contacting doctors, hospitals, and other health care facilities, such a study would be prohibitively expensive and almost impossible to implement.
Scientists at Purdue used a novel approach to show that a molecule called acrolein is elevated in blood and urine from mice with MS-like disease and from people with MS, compared to those without the disease. Acrolein is normally a waste product, but seems to accumulate in people with neurologic disease, becoming toxic to nerve cells. They are now testing whether acrolein levels correlate with disease activity, to determine if this molecule may eventually be used to identify MS with a simple blood test. Medications targeting acrolein are already on the market, raising its potential as a therapeutic target for MS.
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 with secondary progressive MS 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 that was sustained for at least 3 months. Secondary endpoints included reducing the risk of disability progression as measured by the EDSS at six months, 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: The results were originally presented in September 2016 at the ECTRIMS conference. 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 a 23% 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 related 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. More of those taking siponimod than the placebo experienced adverse events (89% vs 82% patients), such as a slower heart rate, high blood pressure, reduced white blood cell counts, macular oedema (swelling at the back of the eye), increased liver enzymes, and increased numbers of convulsions.
Dr. Ludwig Kappos (University of Basel in Switzerland) and a large team of investigators report detailed results of the trial in The Lancet (online March 22, 2018). A commentary about the results by Drs. Luanne Metz and Wei-Qiau Liu (University of Calgary) is also published online.
Comment: “While the magnitude of this response is somewhat modest, it represents a milestone in our unrelenting search for treatments that will benefit people living with progressive forms of MS,” said Bruce Bebo, PhD, Executive Vice President of Research at the National MS Society.
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Background: An important question in the treatment of MS is whether to start treatment for relapsing MS with a powerful therapy at the outset (called induction therapy), or to take a more traditional approach of starting with less powerful therapy and ramping up to a more powerful approach if relapses or other signs of disease activity continue (called escalation therapy).
Researchers from the Karolinska Institute (Stockholm, Sweden) set out to compare outcomes of people receiving induction therapy with a drug called rituximab, which is not specifically approved for the treatment of MS, compared to those receiving escalation therapy with one of the approved disease-modifying therapies. The investigators tracked whether the participants remained on therapy or discontinued it, which is an indirect measure of how well the treatment performed.
Rituximab: Rituximab is a monoclonal antibody (a protein made in the laboratory) that targets a specific protein (“CD20”) on the surface of immune B cells. B cells are known to be involved in the inflammation and damage to the brain and spinal cord in MS. Rituximab is FDA-approved for the treatment of several conditions including some cancers and rheumatoid arthritis, and it has been used “off-label” to treat several immune-mediated conditions, including MS. Rituximab is given by intravenous (into a vein) infusions every six months. A similar B-cell therapy approach that is manufactured differently, called ocrelizumab, was approved by the FDA in 2017 for the treatment of relapsing MS and primary progressive MS.
The Study: The researchers used data from the Swedish MS Registry and medical records of 494 people from two counties in Sweden who had been recently diagnosed with relapsing-remitting MS. About 24% had been started on rituximab; other initial therapies included injectable therapies (such as interferons and glatiramer acetate = 43.5%), oral therapies (dimethyl fumarate =17.4% and fingolimod =3.4%), and natalizumab given by IV infusion (24.3%). The key outcome measured was the proportion of people who discontinued specific therapies.
Results: A higher proportion of people given rituximab remained on it, compared to those who received other initial therapies. The reasons for therapy discontinuation differed by type of treatment, but the most common reasons were side effects, disease activity or pregnancy. The authors also reported a trend for increased relapses and brain lesions in participants using treatments other than rituximab.
This study was funded by the Swedish Medical Research Council and others. The report, by Drs. Fredrik Piehl, Mathias Grandqvist and others (Karolinska Institute), was published online January 8, 2018 in JAMA Neurology.
Comment: Understanding which individuals do best on what therapies is important for enabling people with MS to make the best treatment choices. Unlike well-designed clinical trials that have protocols for patient selection and assessment of outcomes, and that randomly assign participants to treatment groups, this observational study was not able to account for factors that determined why any particular therapy was prescribed for any individual, or for all factors that may have triggered an individual or doctor to discontinue a particular therapy. Results of controlled trials – several of which are now underway – are needed to understand the comparative effectiveness of MS therapies.