“Emerging Therapies for Multiple Sclerosis” was the topic of the
12th annual meeting of Americas Committee for Treatment and Research in Multiple
Sclerosis (ACTRIMS) on June 2 in Washington DC. For the first time, ACTRIMS was
held in conjunction with the Consortium of MS Centers Annual Meeting.
Chaired by Jerry S. Wolinsky, MD from the University of Texas Health Sciences
Center, Houston, ACTRIMS was jointly sponsored by the US National MS Society
and the University of Maryland School of Medicine, in collaboration with the
MS Society of Canada. The complete program is posted online in PDF form at
www.nationalmssociety.org/07ACTRIMSprogram.
Details
The joint CMSC-ACTRIMS Donald Paty Memorial Lecture was delivered by Herman
Waldmann, FRS from the University of Oxford, England. Dr. Waldmann spoke about
prospects
for developing MS therapies that “reprogram” the immune system attack
on the brain and spinal cord that occurs in people with MS. These strategies
might include:
Empowering the body’s own capacity to regulate the immune attack, for example,
by increasing regulatory T cells. “This would allow minimization or even
elimination of immunosuppressive drugs,” said Dr. Waldmann.
Developing agents that inhibit signaling
or migration of attacking T cells.
Using immune system proteins known
as antibodies to temporarily block attacking
T cells. “These can create a ceasefire
during which naïve T-cells [which are
neither disease-causing nor regulatory] can
get recruited into a policing role,” he
added.
Report from the CMSC
For the first time, ACTRIMS was held jointly
with the 21st Annual Meeting of the Consortium
of MS Centers. A poster session held on June
1 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 CMSC focuses on the clinical
care of people with MS. Here is just a small
sample of more than 100 reports on research
to improve the care of people with MS from
this meeting:
Karen Turpin, MSc, BScN from the
University of Alberta, Edmonton, and colleagues
interviewed
41 people with MS living in long-term
care facilities about pain and
pain treatments.
They found that about half were in mild-to-moderate
pain on a continual basis, although less
than 25% remembered being asked to measure
this
pain. The patients rated most pain medications
to be effective; their greatest concern
was related to possible side effects such
as drowsiness
and weakness. These findings might be useful
in guiding pain management in this population.
Trudy Campbell, MN, RN, NP, MSCN
from Dalhousie MS Research Unit, Halifax,
Nova Scotia,
asked 265 people with MS to report on their
social anxiety using several scales. The
investigators found that social anxiety was
common in this
group, and appeared to be unrelated to
the severity of neurological disability.
These
results are important for managing the
comprehensive care of people with MS.
Lynn F. Bloom, MSW from the Rehabilitation
Center, Ottawa, ON, and colleagues reported
on the development of a 5-week wellness
series for people with progressive MS. Individuals
with MS were involved in the design of
the sessions. Topics included spirituality and
personal growth, nutrition and exercise,
assertiveness and mindfulness, and leisure activity. The
results so far indicate that the sessions
were well received by the participants and facilitators,
and a more in-depth evaluation is underway.
Celeste Hunter, MS, CRC from the
University of Washington, Seattle and colleagues
are providing
motivational interviewing (a brief counseling
approach that enhances motivation to change
by exploring and resolving ambivalence)
sessions by telephone to explore whether
people with
MS might use this technique to resolve
employment issues. They have preliminary
data suggesting
motivational interviewing may be useful
in preserving employment and are now conducting
a controlled clinical trial in 60 people
with
MS.
Randolph Schiffer, MD from Texas
Tech University, Lubbock, and colleagues
presented the Goldman
Algorithm, a six-step guideline for identifying
and treating depression in people with
MS, a common symptom. It is designed to be
used
by non-psychiatrists, with backup available
from psychiatrists and psychologists. Clinical
trials are planned to further develop these
guidelines.
Report from the ACTRIMS
Three of the ACTRIMS featured speakers also
focused on monoclonal antibodies (MABs),
laboratory-produced antibodies that can be
programmed to attach to and interfere with
specific molecules to alter the immune response:
Olaf Stüve, MD, PhD from the University
of Texas Southwestern Medical Center, Dallas,
reported on a study in which the safety
and effectiveness of FDA-approved natalizumab
(marketed asTysabri and manufactured by
Biogen Idec)
was evaluated in 23 people for 14 months
after they had undergone treatment in the
course
of clinical trials. In this small study,
the majority of patients remained stable,
no infectious
complications occurred, and immune cell
deficiencies caused by the drug returned to normal.
Bibiana Bielekova, MD from the University
of Cincinnati, reported on immunologic
studies of participants in two phase II studies of
daclizumab (PDL BioPharma and Biogen Idec).
They showed that daclizumab treatment expanded
the population of natural killer cells
-- immune cells that then reduced the numbers of attacking
T cells. Another phase II study in 297
people with relapsing-remitting MS is planned for
this fall in Europe.
Emmanuelle Waubant, MD, PhD from the
University of California at San Francisco,
reported on positive results from recent
studies of rituximab (marketed as Rituxan and manufactured
by Genentech and Biogen Idec) in relapsing-remitting
MS. This drug depletes immune B cells, which
may play a role in the immune attack in MS.
Rituximab is a combination of mouse and human
antibodies. Dr. Waubant noted that “the
next generation” of this agent is under
development, and is more humanized, which
may help to reduce infusion reactions.
Peter Calabresi, MD, from Johns Hopkins University,
Baltimore, is the primary investigator of a
team funded by the US Society’s Promise:2010
campaign to investigate nervous system repair
and protection. He reviewed strategies under
study for protecting nerve fibers in
MS. Although the hallmark of MS is damage to
nerve fiber-insulating
myelin, recent research indicates that damage
to nerve fibers may be the primary factor leading
to progressive disability.
Erythropoietin, a naturally occurring
protein that has been used to treat anemia,
has recently
shown neuroprotective effects.
Sodium-channel blockers may help
to correct abnormalities found in MS in the
tiny
pores along nerve fibers that are essential
for proper nerve impulse conduction.
A component of the myelin sheath
the nerve fiber insulation damaged in MS
called
myelin associated glycoprotein (MAG) may
have neuroprotective effects that can be
reproduced
by administering myelin protein fragments.
Fred Lublin, MD from Mount Sinai School of
Medicine, New York, spoke about the design
of clinical trials as more drugs advance through
the pipeline that are more aggressive and/or
easier to administer. “The outcome measures
currently in use, relapse rate reduction and
time to disability, should be suitable for
a newer generation of immunomodulatory agents,
although increased attention to safety elements
may be warranted,” he said. Dr. Lublin
also noted that advanced MRI technologies may
be of value in assessing underlying tissue
damage and repair for neuroprotective agents,
but that their success will depend on the ability
to make them available at all sites of large,
multicenter trials.
In addition to these featured talks, nearly
50 platform and poster presentations reported
on laboratory and clinical MS research; at
least 22 were funded by the National MS Society’s
research programs.
