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Multiple sclerosis research
progress prominent at ECTRIMS – ACTRIMS joint meeting
September 28 – October 1, 2005
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Medical Update
Advances in multiple sclerosis
research were prominent at the 21st Congress of the European
Committee for Treatment and Research in Multiple Sclerosis
(ECTRIMS), held jointly with the 10th Annual Meeting of
the Americas Committee for Treatment and Research in Multiple
Sclerosis (ACTRIMS), September 28 – October 1, 2005,
in Thessaloniki, Greece. This international meeting fosters
collaboration and cross-pollination between basic and clinical
MS researchers to propel the search for better therapies
and a cure. Following is a selection of hundreds of presentations
reporting progress in the fight against MS. The abstracts
for all presentations are available online.
Clinical Trials
Disease-Modifying Drugs Delay Progression – Dr.
P. Veugelers (University of Alberta, Edmonton) and colleagues
collected data on 1,752 people with MS at the Dalhousie MS
Research Unit between 1979 and 2004. They compared progression
on the EDSS (a numerical scale that measures disease activity)
in these patients before and after disease-modifying treatments
(Avonex, Betaseron, Copaxone and Rebif) became available for
MS. Before the availability of the therapies, the median time
from disease onset to EDSS 4 was 10.4 years and to EDSS 6 was
14.5 years. After MS therapies became available, progression
was delayed to 12.8 and 18.1 years respectively. In comparison,
people who were eligible for treatment but had declined medication
demonstrated the expected rate of progression. (EDSS 4: disability
is present but the person is able to walk without mechanical
or human assistance: EDSS 6: person needs a single cane, crutch,
or brace to walk).
Betaseron Delays Development of
Definite MS – Professor Ludwig Kappos (University
of Basel, Switzerland) and colleagues presented results from
the BENEFIT study, which examined the ability of Betaseron® (interferon
beta-1b, Berlex Inc.) to delay the onset of MS in people
who experience a clinically isolated syndrome (CIS, a single
demyelinating event, putting them at high risk to develop
MS). A total of 487 patients received either Betaseron 250
mcg or placebo for up to 24 months or until MS was diagnosed.
Twenty-eight percent of the Betaseron group had developed
definite MS compared with 45% of the placebo group, and the
development of MS was delayed by 363 days in the Betaseron
group compared to the placebo group. A five-year follow-up
study will assess the impact of early vs. delayed treatment
on the long-term course of MS.
No Benefit – Dr.
D. H. Miller (University College London, Queen Square, UK)
and colleagues administered either Avandia® (rosiglitazone
maleate, GlaxoSmithKline, Inc., a drug used to treat diabetes
which affects hormones involved in the immune response) or
placebo to 51 people with relapsing-remitting MS. No significant
differences were found in tissue damage as detected on MRI,
or in clinical or immunological responses to treatment. Treatment
was well tolerated. The group found no evidence to support
further studies of Avandia in MS.
Early-Stage Therapy Studies
Peptide Therapy Shows Promise – National
MS Society-funded investigator Dr. A. Vandenbark and colleagues
(Oregon Health Science University, Portland) reported on immunological
analysis from a study of NeuroVax® (Immune Response
Corporation) in people with relapsing and progressive MS. NeuroVax
is a vaccine made of protein fragments from a docking site
on the surface of T cells. By examining blood samples taken
from six people before and after three monthly injections,
investigators found that Treg cells – a type of T cell
that can suppress the immune attack – were increased
to a level equal to controls without MS. According to a company
press release, in a subgroup of 12 people, there was a 15%
decrease in the percentage of people with MRI scans showing
active areas of myelin damage at 24 weeks.
T Cell Vaccination Reduces Immune
Cells – Dr. B. Loftus and colleagues (Neurology
Research and Diagnostic Clinic of Houston) conducted an open-label
safety study using two doses of TovaxinTM – T cell
vaccination, an experimental therapy that induces immunity
against T cells that attack nerve fibre-insulating myelin – to
15 people with relapsing-remitting or secondary-progressive
MS. The treatment appeared safe, and T cells reacting to
myelin were greatly reduced in all people in the higher dose
group at five weeks after injection, and reductions were
greater in this group than in the lower dose group at each
of five follow-up visits. A larger study is planned.
Diagnosing/Tracking MS
Possible Diagnostic Marker – Dr.
M. Freedman (University of Ottawa) and colleagues examined
tissue from people who experienced a CIS, 44 of whom went on
to develop MS and 44 of whom developed other neurological diseases.
Levels of the immune system antibody GAGA4 IgM were significantly
higher in people who eventually developed MS. Future studies
will attempt to correlate such findings with MRI and determine
whether this antibody might be used to diagnose and track MS
using a simple blood test.
New Clue to MS-Like Disease – Dr.
S. Pittock and colleagues (Mayo Clinic, Rochester, MN) recently
discovered an antibody (an immune protein that attaches to
and marks molecules for immune attack) in the blood of individuals
with a disorder called neuromyelitis optica (NMO, also known
as Devic's syndrome) that clearly distinguishes it from MS.
NMO was until recently regarded as a severe form of MS. Now,
they report finding areas of myelin damage in the brain tissue
of 36 out of 60 people with NMO. The authors suggest revising
the diagnostic criteria for NMO to include brain involvement.
In recent, related news, this group identified the target of
the antibody as a molecule called "aquaporin 4," a
type of protein that allows for the passage of water (Journal
of Experimental Medicine 2005 Aug 15;202(4):473-7.).
Genetics
Vitamin D and MS –
Dr. G. Mamutse and colleagues (University Hospital of North
Staffordshire Stoke on Trent, Staffordshire, UK) found that
a variation in the gene for the vitamin D receptor, the docking
site that determines how cells receive signals from vitamin
D, was associated with reduced disability in a study of over
500 people with MS who had had MS for more than 10 years.
Recent research indicates a possible link between vitamin
D intake and a reduced risk of MS, possibly explaining lower
rates of MS in areas of increased sunlight exposure, which
results in increased production of vitamin D. Further studies
are needed to confirm these findings.
Immune Genes – Dr.
M. Bartolomé and colleagues (Hospital Universitario
San Carlos, Madrid) found that the gene for early B cell factor,
a molecule important in the development of immune B cells,
was associated with the development of MS in people with another
immune-related genetic variation. This provides further evidence
for the role of B cells in the immune attack in MS.
Immunology
Altered Immune Regulation – Dr.
A. Cross and colleagues (Washington University in St. Louis)
report on a study of immune messenger proteins called
"suppressors of cytokine signalling," or SOCS, which
serve to regulate inflammatory immune messenger proteins. The
group found that levels of SOCS-1 and SOCS-3 were lower in
blood samples taken from people with MS than in those taken
from control subjects without MS. Decreased amounts of these
proteins may allow for the attack on the brain and spinal cord
that occurs in MS.
MS & Pregnancy
Postpartum IVIG –
Dr. J. Haas (Jewish Hospital, Berlin, Germany) reported on
the Gammaglobulins Post Pregnancy in MS Study, a multicentre
European study of IVIG (intravenous immunoglobulins, antibodies
that may modulate the immune system). Investigators administered
two different doses of IVIG to 163 women with relapsing-remitting
MS within 24 hours after giving birth, and every four weeks
thereafter for six months. The women were breastfeeding,
and thus disease-modifying MS therapies were contraindicated.
During the two years before pregnancy, the annual relapse
rate among this group was 1, and the postpartum rate was
similar or less. The results offer evidence of the effectiveness
of IVIG during breastfeeding.
Pregnancy Outcomes –
Dr. V. de las Heras (Hospital Universitario San Carlos, Madrid)
reported final results from the EMPATIE Study on Pregnancy
and MS Therapies, in which investigators reviewed 1,266 clinical
records of 14 European centres since 1995 to identify women
with MS who became pregnant after initiation of immunomodulatory
therapy. Eighty-eight pregnancies were identified in 71 patients;
34.09% were unexpected and 65.91% were planned, with patients
withdrawing from treatment prior to pregnancy. Spontaneous
abortion occurred in 16.67% of those exposed to interferon
beta (unplanned pregnancies) and in 22.41% of those not exposed
(planned) –
both comparable to the general population. These results add
to information on exposure to disease-modifying therapies during
pregnancy.
Multiple Sclerosis Risk
Hepatitis B vaccination review – At
a satellite symposium held prior to the ECTRIMS-ACTRIMS meeting,
a panel of international experts including Dr. Robert T. Naismith
(UK), Prof. Christian Confavreux (France), Prof. Frauke Zipp
(Germany) and Prof. Michel Lanet (France) reviewed the evidence
that some say links hepatitis B vaccines to an increased risk
for multiple sclerosis. Of eight studies that were reviewed
in this presentation, seven showed no significant risk for
people with MS. This includes a Canadian study by Dr. A. D.
Sadovnik (University of British Columbia, Lancet 2000). Just
one study found a link, and it has been criticized because
only 6.7% of the study population with MS had received a hepatitis
B vaccine. The Vaccine in MS study using the European Database
for Multiple Sclerosis (EDMUS) showed that there is no increased
risk of having a relapse following a hepatitis B vaccination
in patients who were relapse free for the 12 months prior to
vaccination. There was no evidence of increased disease activity
on MRI following a hepatitis B vaccination.
ASK MS Information System Code: 2.8.2.q
Disclaimer
The Multiple Sclerosis Society of Canada is an independent, voluntary health
agency and does not approve, endorse or recommend any specific product or therapy
but provides information to assist individuals in making their own decisions.
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