Summary
“Basic and Clinical Research Issues” was the topic of the 15th
annual meeting of ACTRIMS (Americas Committee for Treatment and
Research in MS) on June 5
in San Antonio. This year, ACTRIMS was held in conjunction with
the annual meeting of the Consortium of MS Centers, as well as
the National MS Society’s
Tykeson Fellowship Conference. ACTRIMS was chaired by Jerry S.
Wolinsky, MD (The University of Texas Health Sciences Center at
Houston) and jointly sponsored by the National MS Society and the
University of Maryland School of Medicine, in collaboration with
the MS Society of Canada.
In all, 7 invited lectures and 68 platform and poster
presentations were made at the ACTRIMS meeting; 20 cited funding
from the National MS Society’s research programs. The complete
program is posted to the ACTRIMS Web site at www.actrims.org. Here are some highlights of
select invited lectures and platform presentations at ACTRIMS,
followed by a summary of the CMSC conference:
Details
Stem cell strategies:
The joint CMSC-ACTRIMS Donald Paty Memorial Lecture was
delivered by Neil Scolding, MD (University of Bristol, UK), who
discussed the pros and cons of stem cell therapy for MS. Dr.
Scolding recently reported positive results from a Phase I
safety/feasibility clinical trial of six people with
long-standing MS, who were given intravenous injections of their
own adult bone marrow cells containing a mix of stem cells.
Dr. Scolding commented that our increased understanding of MS has
placed greater demands on potential cell therapies. We now know
that therapeutic strategies need to address nerve fiber damage,
which contributes to the development of disability, as well as
areas of the brain that do not have obvious damage to nerve
fiber-insulating myelin. However, findings in stem cell biology
are keeping pace, giving hope that this strategy will bear out in
an MS treatment. “We now know that bone marrow stem cells are
able to leave the circulating blood stream and enter the brain
and spinal cord, and that they do so in increased numbers when
the nervous system is damaged or disease, as in MS,” he said.
Stefano Pluchino, MD, PhD (San Raffaele Scientific Institute,
Milan) added to the discussion of stem cells, focusing on neural
(nerve) stem cells. Dr. Pluchino’s team has shown that these
cells can reverse the MS-like disease EAE in mice and stimulate
repair of damaged tissues. Dr. Pluchino noted that stem cells
probably do not work just by replacing other cells, but by
orchestrating the activation of several mechanisms, including the
release of immune-modulatory and tissue-supportive molecules.
Tanja Kuhlmann, MD (University Medical Hospital, Münster,
Germany) talked about opportunities to stimulate “endogenous”
repair – the repair capabilities that exist in people with MS,
but that somehow fail to keep up with the damage. She noted
several possibilities for why repair fails: inhibitors, such as
the molecule Lingo-1; the lack of repair-promoting molecules,
such as growth factors; or disturbed signaling pathways.
Strategies for altering these obstructions are under study in MS
models.
Managing treatment risks:
ACTRIMS also featured sessions on managing the apparent increase
in treatment risk in more potent available and experimental MS
treatments, such as the risk of developing PML (a brain infection that has
occurred in people taking the MS drug natalizumab [Tysabri®,
Biogen Idec and Elan]).
Russell Katz, MD, of the U.S. Food and Drug Administration,
reviewed how that agency monitors risk during the process of drug
development. Early on, toxicity in preclinical studies is
evaluated to determine whether an agent is relevant for human
subjects, and might preclude the possibility of human trials.
When clinical trials are completed and the sponsor files for
approval, the agency analyzes the trials information not only to
evaluate effectiveness, but also to determine if the sponsor
adequately defined and considered all aspects of the risks.
Finally, post-marketing studies are often mandated to determine
longer-term risks and how known risks can be managed.
Strategies that may help physicians and patients weigh risks and
benefits of treatments were the focus of several presentations In
a National MS Society-supported study of information materials
related to natalizumab and risks of PML, Sascha Köpke, PhD, and
colleagues at the University of Hamburg and other institutions
across Germany found that after reading the materials, patients
were generally more tolerant of safety risks than neurologists.
The investigators point out the need for unbiased information to
facilitate informed, shared decision making between patients and
their treating physicians.
Treating mental health problems:
David Rintell, EdD (Brigham and Women’s Hospital, Boston) and
colleagues reported on a massive effort to understand mental
health problems in people with MS, funded by a Health Care
Delivery and Policy contract from the National MS Society. Dr.
Rintell’s team surveyed 3,300 people with MS and then queried
1,118 people who reported receiving mental health treatment about
their experiences. Of these, 60% reported having mental health
problems and 14% reported serious mental illness. Of those with
serious mental illness, 44% received no mental health treatment.
Of the 56% who did receive treatment, only half of these received
it from mental health professionals; the others received mental
health treatment from their primary care physician, neurologist,
or a nurse. The results show the need to improve strategies for
identifying and treating mental health problems in people with
MS.
Oral teriflunomide results:
Mark Freedman, MD (University of Ottawa) and colleagues reported
on phase II results of a study in which two different doses of an
oral immune-modulating agent called teriflunomide
(sanofi-aventis), or placebo, were added to ongoing interferon
beta-1a therapy in 116 people with relapsing-remitting MS for one
year. Disease activity as observed on MRI scans was reduced by
86% over placebo in the lower dose group, and by 82.8% over
placebo in the higher dose group. The most frequently reported
adverse events were upper respiratory tract infections,
headaches, and gastrointestinal disorders. Liver enzyme elevation
occurred, not exceeding three times the upper limit of normal.
Larger-scale, phase III studies of teriflunomide are underway in
relapsing MS and in people at high risk for MS.
Report from CMSC Annual Meeting
The
Consortium of MS Center focuses on the clinical care of people
with MS. A poster session held on June 4 featured both ACTRIMS
and CMSC papers, facilitating networking among the many
professionals – basic and clinical researchers, neurologists, and
allied health professionals – attending these meetings. The
full program, with
abstracts, is available online (PDF). Here is just a small sample
of more than 100 reports on research to improve the care of
people with MS, focusing largely on platform presentations:
Cognitive problems:
These occur in as many as one half of people with MS. Sharon
Friedman-Urevich, RN (Winthrop University Hospital, Mineola, NY)
administered paper-based questionnaires and a computerized
cognitive test to 56 people with MS-related cognitive problems.
Results of the computerized tests correlated significantly with
the paper-based tests, indicating that this might be a
cost-effective assessment program that could more easily identify
decreases in cognitive function.
How to measure quality care:
Barbara G. Vickrey, MD, MPH (University of California, Los
Angeles) was awarded a Health Care Delivery & Policy contract
from the National MS Society to define what constitutes quality
MS health care and how to measure it to establish better
standards of care for people with MS. She led a team of MS
specialists and social scientists to analyze the medical
literature. The team then submitted their findings to a group of
15 stakeholders in MS care, including 4 people with MS, who rated
each measure’s importance and impact. The most highly rated
indicators were appropriateness and timeliness of the diagnostic
work-up, bladder dysfunction, cognition dysfunction, depression,
disease-modifying agent use, fatigue, and spasticity. In the
future, these indicators will be further explored in studies to
test new ways of delivering high-quality MS care, and to help
clinicians and healthcare systems in evaluating the quality of
the MS care they are providing.
What stops you from participating in community
programs?
Karon Cook, PhD (University of Washington) and colleagues
administered a questionnaire to 1271 people with MS, asking them
to rate how 15 items affected their community participation: heat
sensitivity, numbness, bowel or bladder problems, imbalance,
problems thinking, sexual dysfunction, slurred speech,
spasticity, swallowing problems, tremor, vision loss, arm
weakness, leg weakness, fatigue, and pain. The strongest
impediments were deemed to be weakness in the legs and fatigue.
Research is needed to test whether interventions for these
symptoms improve community participation.
Fatigue:
This is one of the most common symptoms of MS, occurring in about
80% of people. Marcia Finlayson, MSc, OTR, PhD (University of
Illinois at Chicago) and colleagues studied the effectiveness of
a teleconference-delivered fatigue self-management program in 190
people with MS. The program comprised 6 weeks of 70-minute weekly
sessions delivered by a licensed occupational therapist. Scores
on a scale measuring fatigue and physical function improved
significantly with the program and the improvements were
maintained at 6-month follow-up; mental health showed significant
improvement at 6-week follow-up. Telephone-based interventions
can be an important addition to the fatigue treatment spectrum
for people with MS who have mobility issues. This presentation
won the meeting’s Patient and Family Education Award for Best
Platform Presentation.
Bladder dysfunction:
This symptom occurs in the majority of people with MS. Maria
Lopes de Carvalho, MD, PhD, and colleagues (AISM Rehabilitation
Centre, Italian Multiple Sclerosis Society, Genova) designed
individualized, 12-session urinary rehabilitation programs for 62
people with MS (based on information derived from the individuals
via questionnaires). Urinary incontinence decreased
significantly, as did urinary retention. Further study may show
such efforts to be another addition to treatment options for
people with bladder dysfunction in MS. This presentation received
the Research Award for Best Platform presentation at CMSC.
With information from the National MS Society (USA)