MS and Research 4/21

What’s New in MS Research?
MS is a chronic, unpredictable and often disabling disease of the central
nervous system that affects nearly one million people in the United
States. In recent years, new medications have become available to help
slow the progression of the disease and manage its symptoms.
Researchers continue to piece together new information as they work
toward ultimately finding a cure. Read on about some interesting
findings that have been published in the last 6 months.

The causes of MS are still unclear, however researchers are making inroads into this
important topic. For example, a Danish study recently concluded that children of diabetic
mothers may be at an elevated risk of developing MS. Data showed that MS risk among
individuals whose mothers were diagnosed with diabetes before pregnancy was 2.3 times
higher than those with nondiabetic mothers. Of note, investigators concluded that MS risk
was not significantly affected by having a mother diagnosed with diabetes during pregnancy
or having a diabetic father.

 

Two papers were recently published looking at the role of the microbiome in the
development and progression of MS. A team of researchers from Germany, Spain and
March 2021 Newsletter
TM
ACP Repository

TM Switzerland reported that a protein called “IL-17” (which is

generated in the gut to regulate its microbiome) appears to

be a critical driver in the likelihood of autoimmune disorders
like MS in mice. Another study, also in mice, recently

found that a subset of brain cells (astrocytes) can turn off
inflammation within the brain, based on signals regulated by
the bacteria in the gut. Figuring out how to harness this beneficial activity in humans may
lead to new treatment approaches for MS, including probiotics to alter the balance of gut

bacteria.

Significant progress has been made in the treatment of MS with a wide
variety of oral and injectable disease modifying therapies (DMTs)
available for relapsing and progressive forms of the disease. Two
studies, published in early February, draw conclusions about the
effectiveness of these treatments. The first study suggests that DMTs
are effective at improving disability outcomes in relapsing-remitting
MS (RRMS) over the long term. The second study identified two factors associated with
treatment failure in RRMS. Data showed that DMTs were less effective in subjects who
started treatment when they were younger than 26 years old, or if they had two or more
relapses in the previous year. Interestingly, results suggest that the presence of enhancing
lesions on MRI (which indicate disease activity) did not significantly affect treatment
outcome.
The following research sheds new light on a number of FDA-approved MS treatments. A
small study recently found that intravenous cladribine (Mavenclad) may be as safe and
effective as oral cladribine at reducing relapses, improving MRI activity, and slowing disease
progression in individuals with active MS, with a reasonable safety profile. Further analysis
of data from the EXPAND study recently showed Siponimod (Mayzent) had a significant
benefit on cognitive function in patients with secondary progressive MS (SPMS). A recent
review concluded that treatment with dimethyl fumarate (Tecfidera) was associated with a

higher risk of adverse events, such as flushing, gastrointestinal issues and lymphopenia, over
the short term. More research is required to determine its long-term safety. Ocrelizumab
(Ocrevus), which can be used to treat RRMS, is also the first approved medication for
primary progressive MS. A recent study determined that people with MS treated with ocrelizumab experience lower work and activity impairment than those treated with other DMTs.

Three publications reveal new findings about MS and its treatments in the context of
COVID-19. German researchers published a review of 873 published cases of people with
MS and COVID-19 infection as of December 2020. Results suggest immunosuppressive
therapy itself does not appear to be a substantial risk factor for the virus. With regard to the
different DMTs, the most COVID-19 cases were reported in those receiving anti-CD20
treatment (317 cases). There was a 4 percent mortality rate from COVID-19 infection
among people with MS and 3 percent required ventilation therapy. Severe and fatal cases of
COVID-19 occurred in subjects not taking DMTs, those with previous cardiovascular
diseases, or with higher levels of disability. Researchers suggest that DMTs could be
protective, either directly or indirectly, by reducing MS disease activity. A second study

found that, overall, people with MS have similar incidence, risk
factors and outcomes for COVID-19 as the general population.

Data also showed that subjects treated with an anti-CD20
therapy for a longer period of time appeared to be at a higher
risk of COVID-19 and less than 20 percent developed
antibodies to the virus. Only increased age was related to the severity of COVID-19
infection. Researchers in Croatia identified 33 people with MS who had to delay treatment
with ocrelizumab by approximately one month due to COVID-19. None of the subjects had
a relapse during this period and there were no other clinical consequences from the delay.
Several novel MS treatments are working their
way through the research pipeline, with mixed
results. A clinical trial done at 90 MS clinics
across 13 countries recently showed that high
dose biotin did not significantly improve disability
or walking speed in subjects with progressive MS. Results also suggest this treatment had a
negative safety profile. Researchers at Oregon Health & Science University developed a
compound, called sobetirome, that mimics the myelin-generating effect of thyroid hormone
by stimulating the maturation of its precursor cells (known as oligodendrocytes). New
results show promise for sobetirome’s ability to stimulate the repair of myelin in mice.

German researchers recently published results from a study looking at the effectiveness of an
mRNA vaccine to treat MS in mice. Mice with an MS-like disease were given an mRNA vaccine containing the code for part of a myelin component. Data revealed that the mice

experienced less severe disease than would have been expected and their normal protective
immune responses were not compromised. It’s important to note that early findings in
animal models require considerable study before they can be applied to humans.
Recent advances have also been made in stem cell research.

Italian investigators published a paper in January looking at
outcomes of 210 people with MS who received autologous
hematopoietic stem cell transplantation (HSCT) from 1997 to
2019. Nearly all of them had either RRMS or active SPMS.
After ten years, 65 percent of the subjects continued to
experience no worsening of disability. This rose to 71 percent among those with RRMS.
Researchers from Lithuania conducted a smaller study of 24 subjects with active RRMS that
failed conventional MS treatments and underwent HSCT. Results showed information
processing speed and verbal learning were significantly improved one year after stem cell
therapy. Researchers in Israel and Germany recently published results from a study looking

at the optimal route of administration, and the safety and effectiveness of mesenchymal stem
cell (MSC) transplantation in 48 subjects with active progressive MS. Results showed
treatment with MSCs was well-tolerated and had short-term benefit. Intrathecal
administration was more effective than intravenous administration. A larger clinical trial is
needed to confirm these findings.
We’ve covered the general topic of alternative therapies for MS, cannabis
and the practice of mindfulness in previous newsletters. Recent studies
have shown a number of these unconventional treatments to be beneficial.
Danish researchers recently published results from a study that showed
treatment with medical cannabis oils was safe and well tolerated, and
resulted in a reduction in pain intensity, spasticity and sleep disturbances
in subjects with MS. Investigators in Iran found that 8 weeks of groupbased cognitive hypnotherapy significantly improved the psychological well-being of subjects
with MS. Another study team in Iran looked at the effects of 3 months of cognitive
rehabilitation versus donepezil therapy on memory, attention, depression, and quality of life
in subjects with MS. Subjects on both treatments showed improvement in all areas, however
cognitive rehabilitation was superior altogether. A clinical trial conducted at the Ohio Health Multiple Sclerosis

Center showed that 4 weeks of mindfulness meditation training improved
processing speed above and beyond adaptive cognitive training, or no intervention at all.

While there is no specific diet that will prevent or cure MS, scientists continue to find
evidence that eating certain foods and nutrients, and avoiding others, may help a person’s MS
symptoms and disease activity. In November, Yale researchers published a study suggesting
the abnormal immune system response that causes MS may be triggered by the lack of a
specific fatty acid in fat tissue, called oleic acid. Oleic
acid is found in cooking oils, meats, cheese, nuts,
sunflower seeds, eggs, pasta, milk, olives, avocados, and
other foods. However, it’s important to note that
further study is needed to determine whether consuming
more oleic acid would reduce disease activity in people
with MS. Italian researchers conducted a study looking at the life and dietary habits of 435
people with MS. Their findings suggest the Mediterranean diet may have a beneficial effect
on MS course and disability, and this effect is likely mediated by a change in the gut
microbiome.

It’s a well-known fact that exercise and physical fitness are beneficial, regardless of an MS
diagnosis. Researchers in Canada recently published a review of evidence from animal
models of MS and clinical studies of people with MS that concludes exercise protects and

repairs the brain. The reviewers note that while data suggest that exercise improves brain
and spinal cord structures and functions, there is still much to learn. Another study looked at
physical fitness in youth with MS, and its relationship to disease
activity. Data showed that youth subjects with MS had lower
levels of physical fitness in general, compared with healthy
controls. Those that did moderate or vigorous exercise had
less disease activity and disability.
MS is at least two to three times more common in women than men. There is mounting
evidence that the female hormones, such as estrogen and progesterone, not only affect the
reproductive system, but also the nervous and immune systems. In February, investigators at
the University of California, Riverside, reported that treatment with an estrogen-like
compound, called indazole chloride, repaired damage to myelin, protected nerve fibers from

damage, and partially restored visual function in mice with an MS-like disease. It’s important to note that estrogens impact the reproductive system and have been linked to cancers.

Further study is required to determine if such a treatment would be safe and effective for
people with MS. Another interesting study of nearly 3,000 women with MS concluded that
most of the complications associated with pregnancy (preeclampsia, gestational diabetes,
placenta complications, emergency c-section, instrumental delivery, stillbirth, premature
birth, infants with congenital malformations or low Apgar score) are not more likely in
women with MS. Data suggest that women with MS were more likely to have elective csections, induced delivery, and babies that were small for their gestational age, than women
without MS. The use of DMTs did not significantly impact birth weight. It’s important to
note that this study did not collect information on smoking status, which can impact birth
weights.

Advancements in research are continually shedding light on what causes MS (or makes it
more likely), discovering factors that impact the disease course, and revealing new treatment
strategies. This new knowledge helps to improve the health and quality of life for many
people who live with the disease and is moving us closer to finding a cure. The core of
ACP’s mission is to facilitate research efforts like these, that significantly impact the MS
community.