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 #P337)
Read 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)
