Top-line results were announced of a phase 2 clinical
trial testing an oral anti-inflammatory therapy ibudilast (MN-166,
MediciNova, Inc.) in people with progressive forms of MS.
The results announced in a press release concluded that
ibudilast was well tolerated and significantly slowed the rate of brain
atrophy compared to placebo. Brain atrophy (shrinkage) has been linked to
cognitive and physical disability in MS.
The trial was conducted at the Cleveland Clinic and 27
other sites across the U.S., and involved 255 people with primary or
secondary progressive MS.
The study was principally funded by NeuroNEXT Network,
a clinical trials initiative of the National Institutes of Health, with
additional support by MediciNova, the company that supplied ibudilast. The
National MS Society also provided funding support.
Further details are schedule to be presented Saturday,
October 28th at the MSParis2017 – 7th Joint ECTRIMS-ACTRIMS
These phase 2 results may lead the way to the testing
of ibudilast in larger phase 3 trial(s), which would be needed before the
company could apply for marketing approval from the FDA, the European
Medicines Agency or other regulatory agencies. Ibudilast was designated by the FDA as a “Fast Track Product” which
could speed its future development as a possible treatment of progressive
“These results sound like a very promising step toward a potential new therapy
for people with progressive forms of MS, for whom there are few treatment options,”
said Dr. Bruce Bebo, Executive Vice President, Research, National MS Society.
DETAILS Background: Ibudilast (MN-166, MediciNova, Inc.) inhibits an enzyme
called phosphodiesterase, resulting in suppression of inflammation. While
considered a “New Molecular Entity” in the United States and Europe, ibudilast
is marketed in Japan and Korea to treat cerebrovascular disorders and asthma.
It is being also being investigated in the U.S. for its potential to treat ALS
and drug addiction.
The study was principally funded by NeuroNEXT Network, a clinical trials
initiative of the National Institutes of Health, with additional support by
MediciNova, the company that will supply ibudilast. The National MS Society
also provided funding support because of its focus on progressive MS and
because the trial’s design may answer important questions about the best ways
to measure the benefits of therapies aimed at protecting the nervous system
The study: The trial, known as “SPRINT-MS,” was led by Principal Investigator
Robert Fox, M.D., M.S., FAAN, Staff Neurologist at the Mellen Center for
Multiple Sclerosis at Cleveland Clinic. It was conducted at the Cleveland
Clinic and 27 other sites across the U.S. The trial involved 255 people with
primary or secondary progressive MS. The primary outcome measure was change in
brain atrophy (as measured by an MRI analysis technique called brain
parenchymal fraction) after 96 weeks. Brain atrophy (shrinkage) has been
linked to cognitive and physical disability in MS. Other imaging, safety,
clinical and quality of life outcomes were also measured.
The results announced in a press release from MediciNova concluded that
ibudilast was well tolerated and significantly slowed the rate of brain atrophy
compared to placebo. Further details are schedule to be presented on Saturday,
October 28th at the MSParis2017 – 7th Joint ECTRIMS-ACTRIMS Meeting.
What’s Next? These phase 2 results may lead the way to the testing of
ibudilast in larger phase 3 trial(s), which would be needed before the company
could apply for marketing approval from the FDA, the European Medicines Agency
or other regulatory agencies. Ibudilast was designated by the U.S. Food and Drug Administration as
a “Fast Track Product” which could speed its future development
as a possible treatment of progressive MS.
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
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
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 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.
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
recent studies have suggested that high intake of salt in the diet might
influence MS disease activity and progression, but other studies have not
confirmed that link.
work partly funded by the National MS Society, researchers took advantage
of data accumulated from a previous clinical trial involving 465 people
with possible early signs of MS (CIS) whose salt levels in urine were
measured over the course of 5 years.
found no connection between salt intake and MS activity.
this study does not support a link between high-salt diets and MS disease
activity, research suggests that most Americans eat more salt than is
recommended by federal guidelines. Reducing dietary salt is considered by
most to be beneficial to the heart and circulatory system.
DETAILS Background: Several recent studies have suggested that dietary salt
(sodium chloride) could potentially influence MS disease activity and
progression. For example, one study of 70 people with relapsing-remitting MS,
who were followed for two years, found that higher levels of salt measured in
urine samples were associated with a higher rate of relapses and larger brain
MRI lesions. In addition, mice fed a high-salt diet developed a more aggressive
course of EAE, a laboratory model of MS. But two studies in pediatric MS did
not find a relationship between self-reported salt intake and MS risk or
relapse rates. Resolving this question is important because it offers the
possibility that reducing salt intake might improve a person’s overall health
and their course of MS.
This Study: In work partly funded by the National MS Society,
researchers set out to determine if a high-salt diet is associated with faster
conversion from a first neurologic episode (known as clinically isolated
syndrome or CIS) to a diagnosis of definite multiple sclerosis, or with MS
disease activity. Kathryn C. Fitzgerald, ScD (Johns Hopkins School of
Medicine), Alberto Ascherio, MD, DrPH (Harvard T. H. Chan School of Public
Health) and colleagues took advantage of data accumulated from a previous
clinical trial involving 465 participants who participated in a trial called
BENEFIT (Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial
Treatment) over 5 years. The trial compared benefits of giving interferon to
individuals with CIS early versus later. Each person provided an average of 14
urine samples throughout the five-year follow-up. The researchers estimated
average long-term sodium intake from the multiple urine samples, adjusting for
age, sex, height, weight, where participants lived, and many other variables.
Results: Researchers found that neither average nor high urine sodium
levels were associated with conversion to definite MS. They also weren’t
associated with new MRI lesions at any point in the five years, relapse rates,
or progression of disability. These results suggest that high sodium intake
does not play a major role in influencing MS disease course or activity in
people treated with interferon, at least in the early stages of the disease.
While the study has several strengths, including its length, large sample size,
and systematic collection of data, it has limitations: BENEFIT participants
were treated nearly uniformly with interferon, and the results may not apply to
people on other therapies or no therapy. In addition, participants in the
BENEFIT trial were primarily Caucasian and resided in Europe and Canada, and it
isn’t known if similar results would apply to other populations and
ethnicities. The results also don’t answer the question of whether salt intake
affects the risk of developing MS in the first place.
Comment: Although this study does not support a link between high-salt
intake and MS disease activity, research suggests that most Americans eat more
salt than is recommended by federal guidelines. Even in the absence of direct
evidence that MS immune activity is influenced by salt, reducing dietary salt
is considered by most to be beneficial to the heart and circulatory system.
Read More: Diet, along with exercise, cognitive health, and other
healthy behaviors can make a big difference to how you feel as you deal with
MS. Learn more about living well with MS
Primary progressive MS is
characterized by steadily worsening neurologic function from the onset of the
disease. There are still many gaps in the knowledge we have about what
differentiates relapsing-remitting from primary progressive MS, and the
underlying mechanisms of primary progressive MS. The MS Genetics Group at the
University of California San Francisco is recruiting people with primary
progressive MS for a research study involving a one-time blood sample donation
with the goal of identifying genetic factors driving the course of the disease.
The team also is looking for people without MS who are not related to serve as
controls. The team hopes to identify the major genetic factors that play a role
in disease presentation and progression. Please note: you do not have to be
located in or travel to California to participate. Everything for the study can
be done remotely and is free of charge to participants.
Rationale: Specific subtle variations in the human genome are known to
play a role in determining who is susceptible to developing multiple sclerosis,
and may also influence the course of the disease. People living with MS can
make a difference in studies searching for these genes by donating their DNA
with a blood sample. Identifying the exact location and role of MS genes could
help determine who is at risk for developing the disease and can provide clues
to its cause, prevention, and lead to better treatments.
Details: Once an individual has completed the initial online intake
form, they will receive a call from the study coordinator to discuss details
and answer any questions. The consent form and health information privacy form
can be signed electronically. Participants will then be emailed a link to two
additional short online surveys and sent a blood-collection kit. The kit
includes everything necessary for the blood draw, which can be taken to your
local Quest Diagnostics Lab and returned in a prepaid envelope to the lab at
UCSF. There is no cost to participants.
Contact: To participate or request additional information, please complete a brief
OR you may contact UCSF directly:
Clinical Research Coordinator
UCSF Multiple Sclerosis Genetic Susceptibility Project
675 Nelson Rising Lane, Suite 235A, Box 3206
San Francisco, CA 94158
Toll Free Phone: 1-866-MS-Genes (1-866-674-3637) or Office Phone: (415)
Researchers co-funded by the National MS Society have found that
immune B cells obtained from the blood of people with
relapsing-remitting MS secrete products that can be toxic to nerve cells
grown in lab dishes.
This study offers new insight into how B cells may contribute to nervous system damage in MS.
The team is now conducting further studies to identify the toxic
factor or factors secreted by the B cells, and when and how they may act
in people with MS, and to answer questions such as whether they are
unique to MS, whether they are also evident in people with progressive
Drs Robert P Lisak, Joyce Benjamins (Wayne State University), Amit
Bar-Or (McGill University and currently at University of Pennsylvania)
and colleagues published their findings in the Journal of Neuroimmunology (2017 Aug 15;309:88-99, published online May 17)
DETAILS Background: While scientists still don’t know what
causes multiple sclerosis, they do know that immune-system attacks are
involved, resulting in damage to the myelin that insulates nerve fibers
and to nerve cells and fibers themselves. Immune T cells have typically
been named as culprits, but it has become clear that immune B cells,
another type of white blood cell, are also involved in MS. Research and
studies on B cells, including early studies supported by the National MS
Society, eventually led to successful clinical trials and approval of
Ocrevus™ (ocrelizumab - Genentech, a member of the Roche Group) to treat
people with primary progressive and relapsing-remitting MS. Ocrevus
depletes certain B cells.
The Study: The current study builds on the researchers’
earlier findings that B cells from the blood of people with
relapsing-remitting MS – but not blood from healthy individuals – are
toxic to certain cells that build myelin. In this study, the team
isolated B cells in the laboratory from the blood of 13 women and men
with relapsing-remitting MS who were not receiving disease-modifying
treatment or recent steroids, and 13 controls without MS.
The researchers found that products released by B cells from the people
with MS were toxic to both rat and human nerve cells grown in lab
dishes, while cells from the controls did not incur the same damage. The
nerve cells died from apoptosis – a type of self-destruct program – and
not, as might be expected, from cell disintegration, or from
immunoglobulins (antibodies) that have been identified as culprits in
the MS attack.
Drs Robert P Lisak, Joyce Benjamins (Wayne State University), Amit
Bar-Or (McGill University and currently at University of Pennsylvania)
and colleagues published their findings in the Journal of Neuroimmunology (2017 Aug 15;309:88-99,
published online May 17). This study was supported by the National MS
Society (USA), the Research Foundation of the MS Society of Canada, and
Next Steps: This study offers new insight into how B
cells may contribute to nervous system damage in MS. The team is now
conducting further studies to identify the toxic factor or factors
secreted by the B cells, and when and how they may act in people with
MS. They are using “proteomics” for this work, advanced technologies the
can identify and quantify numerous molecules simultaneously, along with
other approaches. They also plan to answer questions such as whether
the toxic B cells are unique to MS or are found in other immune mediated
disease, which subsets of B cells produce the toxic effects and whether
they are also evident in people with progressive MS.
the U.K. have evaluated additional findings about the immune-system impacts of
Lemtrada® (alemtuzimab, Sanofi Genzyme), a disease-modifying therapy for
treating people with relapsing MS.
team used data from phase 3 clinical trials submitted to the European Medicines
Agency during the drug’s successful approval process. Some of this data was
previously reported at medical meetings and in Lemtrada’s prescribing
their findings, they report that Lemtrada caused long-term reduction of
specific immune cells (memory B and T cells, including regulatory T cells).
They also found that the body rapidly repopulated an overabundance of immature
propose that the blockade of memory B and T cells drives the beneficial effects
also speculate that the known potential side effect for autoimmune thyroid
disease and other autoimmune disorders may be triggered by the overabundance of
immature B cells that occurs when there are few regulatory T cells to keep them
like this one, which reveal more information about a therapy’s mode of action,
are important and may also lead to insights about how to reduce side effects.
Klaus Schmierer, David Baker and others at the Queen Mary University of London
report their findings in JAMA Neurology, published
online June 12, 2017.