What’s New in MS Research: January 2020
Reviewed by MSAA Chief Medical Officer Barry A. Hendin, MD
To live with multiple sclerosis (MS) is to cope with the challenges it presents and to look forward to the promise of ongoing progress in understanding and managing the condition. This edition of “What’s New in MS Research” reflects that mix of obstacles and opportunities.
Highlighting 11 studies, topics range from symptoms associated with MS to strategies for improving quality of life and factors affecting life expectancy. This article also reports on the anticipated expansion of the medications available to treat MS, continued favorable results in stem cell research, promising non-pharmacologic interventions, and more.
As we open not only a new year but a new decade, the prospect ahead is for the opportunities to increase and the obstacles to recede. Researchers such as those whose work is summarized below continue to unlock insights that will enable clinicians and patients alike to make still greater strides in the understanding and treatment of MS.
FDA approves applications for generic versions of Gilenya®
The Food and Drug Administration (FDA) has approved three applications for the first generics of the oral disease-modifying therapy Gilenya® (fingolimod) for the treatment of relapsing forms of multiple sclerosis (MS) in adults.1
The approvals were granted to HEC Pharm Co. Limited, Biocon Limited, and Sun Pharmaceutical Industries Limited. However, due to ongoing legal issues, it is unclear when generic versions of the agent will become commercially available.
Gilenya received FDA approval for the treatment of relapsing-remitting MS in adults in September 2010. In May 2018, the FDA approved use of Gilenya in children and adolescents aged 10 years and older, making it the first drug approved by the FDA to treat MS in pediatric patients.2 (The FDA’s December 2019 approval of generic versions of Gilenya was for the treatment of adults only.)
Another small study on stem cell therapy in MS yields favorable findings
Interest continues among both clinicians and patients alike by the prospect of treating multiple sclerosis (MS) with stem cells obtained from a patient’s own bone marrow. In preparing participants for stem-cell transplantation, physicians generally administer high-dose chemotherapy, radiation, or both to kill cells in the bone marrow. The stem cells are then reintroduced to the patients by infusion, and these transplanted stem cells can then “re-set” the body’s immune system.
While the safety and efficacy of various stem cell treatment strategies are being assessed in relatively large trials, the evidence from smaller studies continues to be generally favorable. One of the latest such inquiries was a Phase I study conducted at the Karolinska Institute in Stockholm, Sweden. The research involved seven patients with progressive MS. 3
When given during clinical remission, the infusions were well tolerated and safe, investigators noted. Five of the seven patients completed a 48-week follow-up period after being infused with their own bone marrow-derived stem cells. At 12 weeks post-infusion, five of the six patients had no new T2 lesions on brain MRI (magnetic resonance imaging).
At the 48-week point, however, three of five patients assessed had such lesions evident on MRI. Meanwhile, all six patients assessed at 12 weeks had stable scores on the Expanded Disability Status Scale (EDSS), while three of five patients had worse scores at 48 weeks. Additionally, evidence of favorable changes in the patients’ immune systems was observed at seven days after infusion. The researchers concluded that the therapy “was safe and well tolerated, and is associated with possible transient beneficial clinical and [immune system] effects.”
A stimulating approach to managing tremor in MS
Just under half of people with multiple sclerosis experience some degree of tremor, with roughly 6% being affected by severe tremor. This is according to a survey of more than 550 participants in the North American Research Committee on MS (NARCOMS) registry. 4
A recent analysis of 13 studies suggests that individuals experiencing tremors may be helped by deep brain stimulation, or DBS.5 This treatment approach involves implanting electrodes within specific areas of the brain. A thin wire connects these electrodes to a pacemaker-like device placed under the skin in the upper region of the chest. The device controls the electrodes’ release of electrical impulses, which can affect certain cells or chemicals within the brain, or counter abnormal electrical impulses.
DBS has been approved by the FDA to treat conditions including epilepsy, obsessive-compulsive disorder, and Parkinson’s disease. It is being investigated for several other conditions, including addiction, chronic pain, dementia, major depressive disorder, traumatic brain injury, Huntington’s disease, and MS.
In analyzing the 13 studies that assessed the impact of DBS in multiple sclerosis, the investigators found consistent evidence that the treatment approach offered benefits as measured by changes in scores on various scales used to measure the degree or severity of tremor. The reported rates of adverse effects in the studies ranged from 8% to 50%.
As researchers, clinicians, and patients continue to address the various manifestations of MS and the impact those symptoms have on quality of life, interventions such as DBS are likely to become the focus of increased attention.
Understanding the prevalence of swallowing problems in MS
A recent Italian study found that a majority of people with multiple sclerosis had dysphagia – or difficulty with swallowing – with one-fourth of them having problems significant enough to require nutritional or dietary modifications.6
More than 200 people participated in the research. The study participants underwent fiber-optic endoscopy, in which a thin scope is used to examine the throat and upper esophagus to assess swallowing function. More than half (58%) of the participants had some degree of dysphagia (difficulty with swallowing), while 26.5% needed to change their approach to eating and obtaining nutrition due to the severity of their dysphagia.
Problems with swallowing were more common in people with progressive forms of MS, who had higher degrees of overall disability, and who were 60 years of age or older.
Although difficulty with swallowing can be a frightening development to contemplate – or report to clinicians – early recognition and intervention can speed adoption of effective strategies. These strategies may include using liquid nutritional supplements, adjusting the consistency of foods and drinks, as well as receiving therapy (through a speech or occupational therapist) to lessen the impact of dysphagia, which can promote long-term wellbeing.
Language impairment also very common in MS
Three-quarters of people with MS participating in a recent international study reported some degree of language impairment.7 Researchers worked with MS-related medical organizations as well as patient advocacy and support groups to recruit 160 people with MS living in various countries. Those study participants completed an online survey, answering questions on speech issues and on quality of life.
Overall, 75% of participants reported some form of language impairment. Those issues included: difficulty with word retrieval (65.7%); difficulty with expressive language (53.8%); difficulty coming up with the names of objects (49.4%); and difficulty with understanding what others were saying to them (40.6%). Please note that some of these problems may also be attributed to cognitive issues.
Investigators found that the prevalence of language issues is not limited to age, gender, educational status, years since diagnosis of MS, country of residence, type of MS, and other factors. Not surprisingly, they also found that study participants with language impairment had a lower health-related quality of life than their counterparts who did not experience this issue.
Noting that, “A decline in language abilities can lead to restricted participation in everyday activities that require communication, including vocational, social, and educational contexts,” the researchers concluded, “frontline healthcare providers need to be aware of potential language impairment in MS and should make timely referrals to speech pathologists for further evaluation and support.” For patients and their families, that translates into reporting any early signs of language issues without delay.
Some good (bien, bueno, bene) news on learning a second language and protecting the brain
A small, MRI-based study suggests that learning a second language may be an effective way for people with MS to stave off the decline in the brain’s grey matter volume (GMV) that is a frequent hallmark of the condition.8
Researchers had 11 people with relapsing-remitting MS and 12 healthy adult volunteers take eight weeks of training in a language other than their first language. Members of the two groups were matched by age and sex. When comparing MRIs obtained before the language training began with follow-up MRIs at the end of the program, investigators found significant increases of GMV in specific areas of the brain (the right hippocampus, parahippocampus, and putamen) of the people with MS.
Further, all study participants had significant gains in listening comprehension, speaking fluency, and vocabulary knowledge. The people with MS also reported improved health-related quality of life. Based on these results, it appears there is something to be said (though perhaps not in English) for learning a second language.
People with MS are more frequently hospitalized for the flu versus those without MS
Investigators from Norway recently published some compelling evidence pertaining specifically to people with MS who acquire the flu.9
Drawing on records for the entire population of Norway – more than 5.2 million people – from 2008 through 2014, the researchers examined how contracting the flu affected people with MS versus those who did not have MS. They found that people with MS were 3.4-times more likely than people without MS to require emergency hospitalization within one week of being diagnosed with influenza.
With several weeks still to go in the flu season, knowing that the risk of hospitalization is greater for individuals with MS who get the flu, members of the MS community may want to check with their doctor to see if getting a flu shot is advised for them.
MS and increased risk for osteoporosis
Researchers in Manitoba, Canada, compared bone density and the incidence of osteoporosis in 783 people with multiple sclerosis (MS) to that of 3,915 healthy controls matched to the MS group in terms of age and gender.10 They found that people with MS had lower bone mineral density than the controls, and were 2.41-times more likely to have osteoporosis. The authors concluded, “These findings indicate the importance of addressing bone health as part of comprehensive MS care.”
With this in mind, individuals with MS may want to consult their physician about having their bone density evaluated. Common treatments for osteoporosis may include calcium supplements, prescribed exercise, and possibly other types of medicines and therapies.
Self-efficacy, physical activity, and enhanced quality of life in MS
Regular physical activity has been shown to enhance physical health, mental wellbeing, and health-related quality of life in people with multiple sclerosis (MS). A recent study of 28 people with MS suggests that having confidence in one’s own ability to achieve desired results, or self-efficacy, when setting goals, serves as an important link between moving more and feeling better.11
The study recruited 18 women and 10 men with varying levels of physical activity. Those study participants completed four separate surveys or similar forms designed to assess the extent of their physical activity, health-related quality of life, self-efficacy in the management of MS, and exercise self-efficacy. Researchers then analyzed the responses, looking for relationships between individuals’ scores on the various instruments.
They found that self-efficacy in goal setting mediated the relationship between physical activity and mental health to a greater degree than a sense of self-efficacy with exercise alone. They concluded, “Our findings suggest that self-efficacy in goal setting can contribute to the adoption and maintenance of regular physical activity for long-lasting times, supporting and increasing the mental quality of life of people suffering from MS.”
Why people with MS miss their doctor appointments
If knowledge is power, a recent study from the Veterans Administration (VA) system may empower clinicians to recognize which patients are at highest risk for missing a significant number of appointments and to take steps to address the underlying causes of that absenteeism. The study drew on three-years’ worth of information from a VA database to examine possible associations between several factors and a patient having excessive missed appointments, which was defined as missing 20% or more of scheduled visits.12
The factors identified by the analysis included distance from the clinic and having a history of post-traumatic stress disorder, congestive heart failure, or chronic obstructive pulmonary disease. None of those factors are particularly surprising, given the challenges they can pose, but validating their importance can help clinicians and social workers become more attuned to the obstacles they represent. As a result, they can flag the need for steps such as helping to arrange transportation or helping to overcome other obstacles.
Looking beyond the VA system, the larger message may be for all people with MS to speak up about any situations that may interfere with keeping their appointments, and ideally avail themselves of assistance.
Mapping the geography of MS risk on a smaller scale
Researchers have long known that multiple sclerosis (MS) is more common in northern latitudes, with potential reasons for this phenomenon, including the reduced amount of Vitamin D-producing sunlight found in those latitudes versus those climates closer to the equator.
Now, however, Italian investigators have reported some intriguing results regarding differences in the prevalence of MS within one region of their country.13 They found that the overall prevalence (or rate of diagnosed people per 100,000 population) of MS in the province of Pavia, which is located in the northern part of Italy, increased from 86 per 100,000 in 2000 to 169.4 per 100,000 in 2016. That doubling of prevalence represents a significantly increased risk.
While the researchers were not able to identify definitive reasons for that increase, they did show that the prevalence varied widely across the province, with several municipalities in the northern part of Pavia having far more cases of MS than other towns and so driving the overall rise in prevalence. They added that their mapping provides a basis for exploring whether environmental or genetic factors may play a role in the higher rates of MS seen in certain towns.
As Americans increasingly examine whether environmental or other causes, or plain random chance, are responsible for “clusters” of cancer cases and other diseases in particular communities, the Italian research may provide the basis for similar MS-related mapping in the United States.
For More Information
For general information or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Questions to MSAA’s Client Services department may also be emailed to MSquestions@mymsaa.org.
Written by Tom Garry, Medical Writer
Reviewed by Dr. Barry Hendin, MSAA Chief Medical Officer
Edited by Susan Wells Courtney, MSAA Senior Writer
References
1 Food and Drug Administration (FDA). FDA approves first generics of Gilenya. December 5, 2019. Available at https://www.fda.gov/news-events/press-announcements/fda-approves-first-generics-gilenya. Accessed January 21, 2020.
2 Food and Drug Administration (FDA). FDA expands approval of Gilenya to treat multiple sclerosis in pediatric patients. May 11, 2018. Available at: https://www.fda.gov/news-events/press-announcements/fda-expands-approval-gilenya-treat-multiple-sclerosis-pediatric-patients. Accessed January 21, 2020.
3 Iacobaeus E, Kadri N, Lefsihane K, et al. Short and long term clinical and immunologic follow up after bone marrow mesenchymal stromal cell therapy in progressive multiple sclerosis–a Phase I study. J Clin Med. 2019 Dec 2;8(12). pii: E2102. doi: 10.3390/jcm8122102.
4 Rinker II JR, Salter AR, Walker AR, et al. Prevalence and characteristics of tremor in the NARCOMS multiple sclerosis registry: a cross-sectional survey. BMJ Open. 2015;5:e006714.
5 Brandmeir NJ, Murray A, Cheyuo C, Ferari C, Rezai AR. Deep brain stimulation for multiple sclerosis tremor: a meta-analysis. Neuromodulation. 2019 Nov 22. doi: 10.1111/ner.13063.
6 Solaro C, Cuccaro A, Gamberini G, et al. Prevalence of dysphagia in a consecutive cohort of subjects with MS using fibre-optic endoscopy. Neurol Sci. 2019.doi: 10.1007/s10072-019-04198-3.
7 El-Wahsh S, Ballard K, Kumfor F, Bogaardt H. Prevalence of self-reported language impairment in multiple sclerosis and the association with health-related quality of life: An international survey study. Mult Scler Relat Disord. 2019;39:101896.doi: 10.1016/j.msard.2019.101896.
8 Ehling R, Amprosi M, Kremmel B, et al. Second language learning induces grey matter volume increase in people with multiple sclerosis. PLoS One. 2019;14(12):e0226525. doi: 10.1371/journal.pone.0226525.
9 Ghaderi S, Berg-Hansen P, Bakken IJ, et al. Hospitalization following influenza infection and pandemic vaccination in multiple sclerosis patients: a nationwide population-based registry study from Norway. Eur J Epidemiol. 2019 Dec 23. doi: 10.1007/s10654-019-00595-2.
10 Bisson EJ,, Finlayson ML, Ekuma O, Leslie WD, Marrie RA. Multiple sclerosis is associated with low bone mineral density and osteoporosis. Neurol Clin Pract. 2019 Oct;9(5):391-399. doi: 10.1212/CPJ.0000000000000669.
11 Guicciardi M, Carta M, Pau M, Cocco E. The relationships between physical activity, self-efficacy, and quality of life in people with multiple sclerosis. Behav Sci (Basel). 2019 Nov 21;9(12). pii: E121. doi: 10.3390/bs9120121.
12 Gromisch ES, Turner AP, Leipertz SL, Beauvais J, Haselkorn JK. Who is not coming to clinic? A predictive model of excessive missed appointments in persons with multiple sclerosis. Mult Scler Relat Disord. 2019 Nov 9;38:101513. doi: 10.1016/j.msard.2019.101513.
13 Bergamaschi R, Monti MC, Trivelli L, et al. Increased prevalence of multiple sclerosis and clusters of different disease risk in Northern Italy. Neurol Sci. 2019 Dec 23. doi: 10.1007/s10072-019-04205-7.
