Hollie & Art's ECTRIMS 2008 Notes

Each year, Hollie and Art try to attend several big MS and Neurological conferences. One of the big MS conferences is ECTRIMS (European Committee for Treatment and Research In MS), and this year it was held in Montreal. We attended as many sessions as we could, took notes, and wrote them up for you to enjoy.

If you are interested in the latest research in MS, you'll want to slog through this long posting.

continued...

ECTRIMS - Montreal, Canada
Art Mellor & Hollie Schmidt - September 17, 2008

This year ECTRIMS wasn't in Europe (which is what the "E" stands
for). It was a joint meeting with ACTRIMS and LACTRIMS (Americas and
Latin America) and held in Montreal. While we didn't get the fun of
experiencing another European country, we didn't get the misery of
experiencing jet lag either! Much more conducive to not nodding off
during endless talks in dark rooms... and therefore much better for
note-taking.

We flew up Wed morning and arrived to the most empty Customs area we've
ever seen. Straight out to our hotel, then off to our traditional
first meal in another country - McDonalds - so that we can take a
picture of Hollie eating at McDonalds in another country. Sad,
yes. But fun and tasty.

Wednesday 09/17/2008:

*** Satellite Symposium -- Methylation and Remyelination:
Epigenetic activation of remyelination in adult brain *** (Art/Hollie)

Epigenetic memory loss in aging oligodendrocytes: a message for
multiple sclerosis (Patrizia Cassacia-Bonnefil)

This was the first of a few talks we heard that dealt with factors
that affect remyelination -- definitely a important topic in MS. This
speaker has studied factors that inhibit oligodendrocyte precursor
cells (OPCs) from developing into oligos and is investigating how
these inhibitors are expressed. It turns out that changes to histone
(the protein that the DNA strands of our chromosomes wrap around)
affect the expression of these inhibitors. Some of the factors that
affect histone wrapping (e.g., HDAC1 and YY1) have been found to be
altered in MS brain tissue vs. control tissue, suggesting that
remyelination may be less efficient in MS vs. controls. Still to be
investigated is whether levels of these particular proteins are
correlated with the extent of remyelination in MS brains.

--
Exogenous methylation and the suppression of murine
demyelinating disease: a new strategy for treatment of MS (Fabrizio
Mastronardi)

Enzymes called PAD (peptidyl arginine deiminase) control a process
called citrullination that alters proteins. The enzymes PAD2 and PAD4
have been shown to citrullinate MBP which affects its charge and
destabilizes it. PAD2 expression is increased in MS white matter,
leading to greater MBP citrullination. A small molecule called 2-CA
can inhibit PAD enzymes and in conjunction with vitamin B12 has proven
beneficial in EAE and other mouse models of neurodegeneration.

*** Young Researchers 1 *** (Art/Hollie)

Assessment of Theory of Mind and emotions in MS (A Henry)

"Theory of Mind" is something that develops throughout childhood and
has to do with the ability to think about your own and other people's
thoughts and beliefs. Dr. Henry wanted to know whether this was
affected in MS. She did find that people with MS did score lower than
controls on some theory of mind tasks, as well as some facial
expression recognition tasks. She didn't find any association between
performance in these two areas, or with demographic factors or fatigue
or depression. This type of impairment could affect the social
behavior of people with MS.

--
MR & neuropsychological features help predict disease course in benign MS (E Portaccio)

Benign MS is typically defined as an EDSS < 3.0 at 15 years or EDSS <
2.0 at 10 years. A research team monitored a group of people with
benign MS for five years, after administering MRIs and neuropsychological
tests. After five years, 30% were no longer benign. Analysis of the
initial test data revealed that being male, having failed at least two
of the NP tests, and having higher T1 lesion volume were predictors of
progressing to an EDSS of at least 4.0.

--
Increased CSF osteopontin concentrations in MS attacks (L. Bornsen)

Osteopontin (OPN) is a protein that helps regulate inflammation. Minor
increases in OPN concentrations in the CSF were seen in people with
RRMS and CIS vs controls when the cases were having relapses (with
RRMS > CIS > controls). Levels dropped back to normal after resolution
of the relapse. Increases in OPN in serum were not seen. This could be a
weak MS biomarker.

In another study, plasma OPN increased after 6 months on Copaxone or
after a course of steroids. No changes were seen with interferon.

--
Serum Vitamin D25 status as a determinant of MS outcome in kids with CIS (H Hanwell)

117 kids who presented with an initial demyelinating event were
followed. 19 converted to MS (mostly older kids, mostly female). The
mean Vit D level of those who did not convert was 61.3 nmol/L vs 44.2
in those who converted. Normal is considered 75. This is yet another
association for Vit D and our good friend MS.

--
Altered fMRI activity in hippocampal subregions during verbal
learning in MS (K Kern)

They found that verbal memory issues correlated with hippocampal
atrophy in people with MS. This is more a finding confirming what was
already "known" about the brain using MS as a "funky brain" to study.

*** Satellite Symposium -- Teriflunomide: Progress in the development
of an oral medication for multiple sclerosis (sponsored by
Sanofi-Aventis) *** (Hollie)

--
Rationale for development: mechanism of action and pre-clinical
research (Reinhard Hohlfeld)

Teriflunomide inhibits the proliferation and function of activated
lymphocytes (but not resting lymphocytes). New data from Dr. Jean
Merrill showed some impressive results in chronic relapsing EAE when
the drug was administered either at onset or after the disease was
active: only 6% myelin loss vs. 85% in control mice; only 4% axonal
loss vs. 67%; no MRI enhancement indicating blood-brain barrier
preservation. Of course we have to remember this is only EAE, but
trials are underway to see if these effects are just as strong in MS.

--
Clinical data (Mark Freedman)

Dr. Freedman reviewed the results of a phase 2 proof of principle
trial. This trial included 207 MS subjects who were on 7 or 14 mg
doses of teriflunomide or placebo for 36 weeks. The numbers of unique
active MRI lesions were significantly lower in the treatment arms
(1.04 and 1.06 vs. 2.68 for placebo). Some clinical efficacy
indications were seen but this study was too small to demonstrate
these conclusively. An extension phase where the treated subjects
stayed on their dose and the placebo group was randomized to the two
treatment doses produced similar results. Adverse events were
similar in the two groups although white blood cell counts were lower
and liver enzymes were higher in the treatment groups. More common
AEs included heartburn, upset stomach, and skin rash.

--
Teriflunomide development plan; moving forward (Aaron Miller)

Dr. Miller outlined the upcoming phase 3 teriflunomide trials. TEMSO
will include 1,088 relapsing MS subjects, will last for 108 weeks,
will evaluate relapse rate, progression, MRI, and safety/tolerability,
and will be placebo-controlled. TOWER will include 1,110 subjects,
will have a variable duration (minimum 48 weeks), will evaluate
clinical endpoints, and will also be placebo-controlled.

TOPIC will include 780 CIS subjects, will run for 108 weeks, and will
evaluate conversion to MS as well as relapse rate, MRI, and
safety/tolerability. Other trials in the works include one where
teriflunomide is compared to an active drug (instead of placebo) and a
phase 2 trial of teriflunomide in combination with interferon and
glatiramer acetate.

--
Questions and answers

Q: Does teriflunomide affect FoxP3 regulatory T cells?
A: We don't
know that yet.

Q: Is there any evidence for a rebound effect after the drug is
stopped?
A: No evidence of that was seen in EAE mice, and the drug's
effect seems to persist for a few days.

Q: Is there any evidence for a direct effect on the central nervous
system?
A: We don't know of one.

Q: Was any effect on progression seen in the phase 2 trial?
A:
There was a trend in favor of the high-dose group, but this is
unconfirmed and was not statistically significant. The
placebo-controlled period was too short to really demonstrate an
effect.

Q: Is there any risk of teratogenicity (birth defects)?
A: There was
one pregnancy in the phase 2 trial, which resulted in a healthy birth,
but animal studies suggest a possible risk of birth defects so use of
two contraceptives is called for.

Q: Why was it necessary to have both TOWER and TEMSO?
A: The FDA is
reluctant to approve drugs without two phase 3 trials.

Q: Is it ethical to conduct placebo-controlled trials now that there
are effective drugs?
A: Yes, if you include only people who decline
use of these drugs or can't tolerate injectibles. You have to really
make sure though that they have considered all their options carefully.

Q: Is there any evidence of opportunistic infections with this drug?

A: None to date.

*** Young Researchers Session 2 *** (Hollie)

Diffuse inflammatory changes in MS normal appearing white matter
(Marco Vercellino)

The purpose of this tissue study was to characterize MS normal
appearing white matter, distant from MS lesions. In the NAWM samples
studied, there were signs of microglial activation but this wasn't
full-blown. No such activation was seen in samples from non-MS
controls. There was no overt blood-brain barrier (BBB) alteration in
the MS samples but there was diffuse expression of VCAM-1 which would
allow T cells to infiltrate into the white matter. Inflammation was
also seen in ALS and Alzheimer's samples, but not to the same extent.
Also observed in the MS samples were axonal dystrophy, acute axonal
damage, axons staining positive for IgG, and axonal spheroids
indicating transection. There was diffuse microglia and macrophage
expression of progranulin, which is a neurotrophic tissue repair
factor. Perhaps the inflammation found in NAWM reflects (at least
partly) an attempt at neuroregeneration?

--

USPIO-enhanced MRI demonstrates diffuse inflammation in MS NAWM
(Machteld Vellinga)

USPIOs are tiny iron-containing particles that are used to track
macrophages via MRI (macrophages gobble them up and are then visible
on MRI). They are just now being used in human studies to show the
infiltration of macrophages into different tissues such as the brain.
In this study, 8 RRMS, 7 PPMS, and 5 control subjects were given MRIs
both before and after injection of USPIOs. The images did reveal
enhanced presence of the USPIOs in the MS brains. Next steps are to
see how USPIO results correlate with clinical values and see if being
on treatments thought to affect inflammation can affect USPIO results.
Someone asked whether the altered MRI results reflect increased
perfusion in the MS brain rather than macrophage infiltration of the
brain. Dr. Vellinga said that was a possibility, but results on
perfusion have been mixed, with many studies showing reduced perfusion
in MS brains.

--

Identification of a factor inhibiting nucleocytoplasmic
transport and differentiation within preserved oligo precursor cells
in MS: a possible cause of remyelination failure (Jin Nakahara)

Dr. Nakahara is interested in learning what's wrong with OPCs in MS --
why do they fail to differentiate. Her work has revealed that a
protein called TIP30 is overexpressed in MS OPCs, and is potentially
interfering with another protein called Importin-b involved in the
differentiation process. This theory is supported by the relative
lack of TIP30 in remyelinating shadow plaques, and by the creation of
a TIP30-transfected OPC cell line which was susceptible to cell death
and did not differentiate after contactin stimulation. If we could
block TIP30, it might help with remyelination; however, inhibition of
TIP30 might promote tumor formation. However, overexpression of TIP30
might be induced by environmental factors, so perhaps these factors
could be found and diminished in some way.

--

*** Satellite Symposium -- Contemporary Approaches to MS Management
(Sponsored by Bayer) *** (Hollie)

This symposium featured a panel of MS experts who were assigned to
answer questions posed by neurologists all over the world (presented
in the form of whizzy videos).

Q: Should CIS be treated? If we treat CIS in a patient and there are
no more relapses, how do we know it was really going to be MS?
A (from Flavia Nelson): She presented some data that didn't really
answer the question, but at the end she said she wouldn't
automatically treat every case of CIS. Some cases she would monitor
instead, perhaps doing more work to rule out other diseases. Someone
from the audience asked how long to treat a CIS patient who is doing
fine, but if there was a clear answer I missed it.

Q: What should we do with patients who have MRI lesions but no
clinical episodes? A (from Ching-Piao Tsai): He showed an example of
an MRI with lots of lesions and said he would treat this case (and
reiterated when questioned by an audience member that yes, he would indeed
treat a "clinically absent" patient).

Q: Should we use disease-modifying therapies in SPMS patients with
relapses? A (from Ching-Piao Tsai): Yes, four trials have shown
reduced relapse rate, MRI lesions, and/or progression when using IFNb
in SPMS patients.

Q: Should MRI be used to help monitor for suboptimal treatment
response? A (from Tony Traboulsee): That seems sensible, but you
have define what threshold you're going to use to define
non-response.

Q: How often should you perform MRIs on MS patients? A (from Tony
Traboulsee): (1) Prior to treatment start, (2) prior to switching
treatment, (3) when an unexpected decline happens, (4) if something
occurs to make you question the diagnosis. He also reminded the
audience to assess cognitive changes since these can be significant
but aren't captured by the EDSS.

Q: How should breakthrough disease be defined and treated? A (from
Alberto Gabbai): He defines clinical breakthrough as >1 relapse/year or
incomplete recovery from relapse. He considers an MRI breakthrough to
be a new spinal cord or brainstem lesion. Treatment options include
mitoxantrone (perhaps followed by an immunomodulator),
cyclophosphamide, monoclonal antibodies, perhaps even bone marrow
transplants or combination therapies although these are experimental.
An audience member asked about pulsed steroids, and Dr. Gabbai says he
seldom uses them for breakthroughs, preferring to use cyclophosphamide.

Q: What do you tell patients who want to go on a drug holiday? A
(from Xavier Montalban): There is little evidence for or against
taking drug holidays. For example, the evidence of a rebound effect
from stopping Tysabri is mixed. His best guesses are that disease
activity will probably return to pretreatment level; that the longer a
person has been treated, the longer period they will have without
disease activity; there shouldn't be a rebound effect with IFN-b; and
in general, short holidays may be OK. He has female patients go off
their drugs when trying to get pregnant, and his impression is that
their MRIs are mostly stable for at least 3-5 months. An audience
member asked whether Tysabri patients should stop taking it after two
years. Dr. Montalban said he's had patients on it for four years, and
he is monitoring them carefully but there is not much data saying they
should automatically stop. Another audience member asked whether he
advises women with MS to go back on therapy after giving birth.
Dr. Montalban said that he recommends that they concentrate on taking
care of their baby and not quit breastfeeding just to go back on
therapy.

Thursday 09/18/2008:

*** Plenary Session 1 *** (Art/Hollie)

--
The changing frame of MS over the centuries (Jock Murray)

Dr. Murray gave an overview of how MS has been thought of and treated
since the 1800s when it was first really recognized and studied as a
disease entity. We learned that France after the French Revolution
was the place to really learn about medicine since med school
professors were made to work at hospitals and built up large clinics
there. Dr. Murray's presentation was facilitated by none other than
Dr. Jean-Martin Charcot himself, who came forward in time to present
snippets of his famous 1868 MS lectures. (Or maybe it was just an
actor in period costume with a dry ice machine? Hard to say.)

--

*** Parallel Sesson 1: Neurodegeneration & Inflammation *** (Art/Hollie)

--
Evidence for primary neurodegeneration (W Bruck)

Both this and the next talk were supposed to present the argument that
neurodegeneration precedes or follows inflammation in MS. Both
presenters failed to make a coherent argument in our opinion.

Evidence presented: CD8+ T cells can transect axons; 60% axonal loss
has been seen in some chronic lesions, antibodies in the CSF that
recognize axons, some MS lesions show dissociation of axon/myelin
pathology, mitochondrial dysfunction seen in axons, axonal damage
without demyelination seen in some EAE lesions (possibly not relevant
to humans), gray matter (less myelin) involvement. However, Dr. Bruck
said he does not believe that there is neurodegeneration in MS that is
independent of immune attacks. For example, mitochondrial
dysfunction could be due to the presence of nitric oxide.

--
Evidence for secondary neurodegeneration (W Moore)

This talk was even less convincing in our opinion. We failed to see any
form of argument, just a series of statements about findings in MS:

Wallerian degeneration can kill axons, immune responses can kill
axons, BBB breakdown (not sure what this has to do with it),
demyelination, ion channel insertion can kill axons.

Both talks can be summed up by saying there are different things
present in the MS brain environment that can harm axons, and these can
result from immune activity and/or loss of myelin.

--
Homogeneity of active demyelinating lesions (E Breij)

This research team looked at autopsy material from 66 people with
established MS. They investigated a host of immune markers in lesions
and found features that were in virtually all active demyelinating
lesions involving complement and IgG (indicating a dominant role for
the humoral immune system in demyelination in established MS). This is
in contrast to the "4 types" study by Lucchinetti et al at the Mayo
clinic that found antibodies and complement in only 50% of their
subjects. They then went back and looked for the various differing
markers that Luccinetti had found, but did not see them in their
samples. For example, these was no preferential loss of MAG,
consistently low markers of hypoxia-like tissue damage, and only rare
signs of oligo apoptosis. So there was no evidence for the "4 types"
heterogeneity in this set of samples, but these were all autopsy
samples from people with established MS, whereas the Mayo study also
included biopsy samples. Therefore these results do not necessarily
contradict the earlier results.

One member of the audience suggested that they need to send blinded
samples to both groups and see what sort of results they get. I'm sure
they'll jump right on that. :-)

--
Progression of brain atrophy is similar in drug-free MS
sub-types (A Giorgo)

This study analyzed MRIs from 963 untreated people with CIS, RRMS,
SPMS, or PPMS who had at least 2 MRIs at least 12 months apart
(largely placebo controls from clinical trials). Snazzy new computer
aided techniques were used to measure brain volume and normalize
subjects for comparison. It was found that across all types the
atrophy rate was about 0.5% per year (vs about half that for the
general population). There was a weak correlation with age and EDSS,
but not MS type or symptoms. These results indicate that brain volume
loss in MS steadily progresses regardless of course or disease
duration.

An audience member pointed out that studies of *treated* MS subjects
have found higher atrophy rates than the ones presented here -- the
speaker postulated that this discrepancy might be due to differences
in methodology.

--
Treatment with Copaxone protects axons in CIS (D Arnold)

This was an MRS (Magnetic Resonance Spectroscopy) sub-study of the
PreCISe trial. Whereas MRI measures water content, MRS was used to
measure the presence of molecules Cho, Cr, and NAA - which are markers
of cell injury which correlate fairly well with disability.

At one year they saw a positive benefit of Copaxone, but at two years the
results were not statistically significant (which the speaker claimed
was due to small sample size at two years).

--

*** Satellite Symposium -- Improving the course of MS: Treat today
for a better tomorrow (sponsored by Teva & Sanofi-Aventis)*** (Hollie)

--

Giancarlo Comi presented results from the PreCISe trial which analyzed
whether Copaxone could delay a second clinical event in CIS subjects.
This trial had 481 subjects and included a placebo arm. It was
supposed to run for three years with a two year open label phase.
However, it was stopped early because a positive effect was seen,
making use of the placebo arm no longer ethical.

Use of Copaxone delayed clinically definite MS by an average of 386
days and reduced the risk of converting to MS by 45%. (These numbers
were determined at the point when 25% of the subjects had converted.)
Reductions in new T1 and T2 lesions were also seen in those converters
who were on Copaxone vs. placebo; atrophy data is still being
analyzed. No new safety issues were identified. Dr. Comi that CIS
trials are also being performed/planned for teriflunomide, cladribine,
and IFN-b1a subcutaneous.

An audience member asked whether Copaxone is the best choice for CIS
given its safety and efficacy. Dr. Comi replied that only a
head-to-head trial of Copaxone vs. the interferon drugs would resolve
which is most effective, since you can make the case for either option
depending on how you look at the data. However, Copaxone and the
interferon drugs appear to have similar safety profiles.

Robert Zivadinov next gave an overview of emerging MRI techniques that
may be used in the future to evaluate drug efficacy, and Xavier
Montalban reviewed evidence that Copaxone may be neuroprotective.

--

*** Parallel Session 3: Brain Plasticity & Repair *** (Art)

--
Myelin repair in CNS: role of guidance molecules (C Lubetzki)

It is known there are inhibitors of OPC (oligodendrocyte precursor
cells) maturation and remyelination, but it is also possible that
there is a dysregulation of guidance molecules such as Sema 3A and
3F. These are molecules that direct OPCs toward/away from areas that
need remyelination.

Looking at mRNA from MS brain autopsy material, they saw that Sema 3A
and 3F were upregulated. Sema 3A prevents recruitment and is
upregulated after demyelination. Thus they conclude that it might make
a good drug target.

--
Axo-glial interactions: role of transporters & glutamate
receptors (P Stys)

It was at this point that I started to lose my ability to understand
what the presenters were talking about. The jargon was flying hard and
fast and it was all about the mechanics of axon/glia operation. I did
not get a single point made in this talk.

--
New observations on the mechanism of myelin wrapping (D Colman)

This talk presented some cool new nanotech stuff used to grow live
neurons and oligos for better study. I never really noticed any
discussion of myelin wrapping however...

--

The next two talks were EAE related and rather opaque. I didn't get
the impression I missed anything important and I left before the last
one was over as the session was running more than 20 minutes late and
I had to go meet Hollie.

*** Parallel Session 4: Antibodies: From pathogenesis to treatment *** (Hollie)

--
What is the evidence in humans that auto-antibodies to CNS
antigens are pathogenic? (Jeffrey Bennett)

Dr. Bennett reviewed evidence that antibodies play a role in the
pathology of MS. However, there does not appear to be one specific
antibody target (like a particular myelin protein or lipid) that can
be identified consistently in serum, CSF, brain tissue, etc. from MS
subjects. He highlighted a recent study where antibodies were derived from
single B cells from the CSF of eight MS subjects -- these antibodies did not
bind to MOG, MBP, or PLP.

--

Monoclonal antibodies: the future (Steve Hauser)

The first part of this talk focused on Rituximab (Rituxan) which is an
antibody that targets CD20 which is expressed on B cells. Because the
drug leaves antibody-producing plasma cells alone, and appears to
start working before these cells can die out, its effect is unlikely
to be due to decreased autoantibody production. Instead, its effect
may have to do with other B cell functions such as antigen
presentation, cytokine production, and/or recruitment of other cells
to sites of inflammation.

A hypothesis that comes from rheumatoid arthritis is that sets of B
cells that come from the same cell line and express variations of the
same antibody transfer back and forth between target organs and
lymphoid tissue. Evidence for this comes from the identification of
the same sets of B cells in different locations, and in fact the same
B cell clones can be found in different lesions from a single MS
subject. Rituxan seems to target mobile B cells and therefore may
work by preventing B cells from reaccessing target tissues.

Also reviewed were other monoclonal antibodies that target various B
cell surface molecules, block growth/survival pathways, and/or
interfere with germinal center interactions.

--

Lipids as autoantigens and therapeutic immune modulators in MS
(Peggy Ho)

This talk focused on lipid reactivity in EAE. Co-immunizing with one
lipid, sulfatide, worsens EAE, but co-immunizing with certain other
lipids seems to improve it.

--

Alterations in CSF chemokine pattern following B-cell depletion
with rituximab in relapsing MS patients (Anne Cross)

Washington University researchers performed a phase 2 Rituxan trial in
2002 in MS subjects who did not respond to other drugs. Dr. Cross
presented the results of CSF analyses resulting from this trial:
* No change was seen in oligoclonal band numbers, IgG index, Ig levels
* CSF B cells were depleted
* There were changes in the proportions of the types of B cells that remained
* T cell numbers were also reduced by more than 50% on average, maybe
due to having fewer B cells to attract them? This seems plausible
based on lower levels of chemoattractants in the CSF.

--

Molecular characterization of CSF B-cell response in MS (Jerry Lin)

Dr. Lin described a study that showed that B cell clonal lines can
persist in an MS subject's CSF over time. Follow-up work is being
done to explore what the target of this B cell is -- this includes
screening its antibodies against brain and spinal cord material,
Epstein-Barr virus antigens, etc.

--

At the end of the day Hollie and Art met with the folks from
Glycominds. They are using samples from our repository to develop a
novel MS diagnostic involving antibodies to glycans. We've never met
in person, so we all went out for a beer.

Friday 09/19/2008:

Art had to fly to Denver Friday morning for a fundraising event,
so I (Hollie) was on my own for the rest of the conference. Not being
able to clone myself or be in two places at once, I wasn't able to
attend every session, but I did my best to cover as much as I could.

*** Oral Fingolimod: From innovative science to clinical promise *** (Hollie)

--
What we have learned from phase 2 and 3 studies in RRMS (Ludwig Kappos)

Fingolimod (aka FTY720) is Novartis's experimental oral MS drug.
Dr. Kappos reviewed the status of its clinical trials. Two phase 3
studies are currently underway -- TRANSFORMS and FREEDOMS. These are
large studies (1,292 and 1,272 subjects) that are comparing fingolimod to
placebo and interferon-beta. Results will be available in 2009 and
2010.

Two deaths have occurred during these trials, both due to infection.
One subject died of HSV-1 encephalitis, the other one of varicella
zoster infection. The study team is not sure what role fingolimod
played in these deaths, but they have expanded the monitoring of trial
participants.

Dr. Kappos also reviewed phase 2 results which included a 50%
reduction of relapse rate and an 80% reduction of MRI disease activity.

--

S1P receptor modulation: effects on the immune and central
nervous system (Jerold Chun)

This was a review of how fingolimod affects cells in the body. Ready?
Here goes: Phosphorylated fingolimod binds to S1P receptors that are
expressed on lymphocytes and in the CNS. In lymph nodes, lymphocytes
normally follow S1P molecules to leave the node and return into
circulation, but fingolimod results in downregulation of S1P receptors
so the cells don't leave. This effects naive T cells, B cells, and
proinflammatory central memory T cells, but effector memory cells can
still leave (these are immunosurveillance cells stationed throughout the
body).

In the CNS, S1P receptors are expressed on astrocytes, neurons,
oligos, and microglia. Fingolimod can cross the blood-brain barrier
and according to animal studies, may reduce astrogliosis which is
known to inhibit repair mechanisms such as remyelination. Jack Antel
also pointed out that researchers are also studying whether fingolimod
has a direct effect on oligos as well.

--

Oral fingolimod : Phase 3 in PPMS (Alan Thompson)

Dr. Thompson described the features of a new study of fingolimod in
PPMS subjects (INFORMS). 650 subjects will be enrolled; they must
have an EDSS between 3.5 and 6, with evidence of progression in the
past two years. Endpoints include progression as measured by EDSS,
timed 25-foot walk, and/or 9-hole peg test. Also to be evaluated are
MRI markers and exploratory prognostic biomarkers. The trial will
last 36 months and will be placebo-controlled.

An audience member commented that fingolimod may actually be
counterproductive in progressive MS because immune cells may be
trapped in the brain, and unfortunately there is no good animal model
to test this possibility with in advance.

--

***Plenary Session 2: What can we learn from treating MS? (Chris
Polman) *** (Hollie)

Dr. Polman reflected over his years of treating MS and conducting
trials, and produced some pearls of wisdom:

* Analyzing clinical trial results in terms of subgroups can be
informative; for instance, results can differ between people
depending on whether they have Gd+ lesions, or depending on what
country they're from. These analyses can sometimes reveal
information about disease mechanisms.

* Results between different studies can vary widely making it
difficult to compare studies. You can find support for any claim
you want to make just by choosing the right studies to compare.

* Withdrawal effects have been seen for some drugs, which complicates
matter if you're using a cross-over design.

* Keep an open mind even when results are disappointing, because they
can still teach you something.

* Growing use of clinical research organizations in trials increases
speed and efficiency, but perhaps at the expense of information and
insights.

--

*** Parallel Session 5: Advances in imaging techniques (Hollie)

OCT: Window on MS (Laura Balcer)

This talk reviewed the use of optical coherence tomography, an imaging
technique for assessing optical nerves and eye structures, in
evaluating MS. It's a non-invasive, quick technique that can
visualize non-myelinated axons and neurons. OCT results have been
shown to correlate with function, MRI images, and tissue findings. It
is currently being assessed for use in observational studies and
clinical trials.

--

New insights into MS pathogenesis based on post-mortem MRI
studies (Frederik Barkhof)

This was another review of why scanning post-mortem brain tissue and
comparing it to what you then find when examining the tissue can be
useful. Some uses include guiding your sampling of the tissue, and
validating new MRI techniques.

I'm going to insert a little rant here -- most of the sessions I
attended started out with a few talks like this where the organizers
invited speakers to review a subject. I would much rather have heard
more about new findings than summaries of what's already been done.

--

Whole brain magnetization transfer histogram metrics predict
clinical disability in MS patients: a 5-year follow-up study (Nancy
Richert)

Dr. Richert's team at the NIH has followed a cohort of 31 RRMS
subjects for five years or more, performing annual MRIs on them. At
the beginning of the tracking period, their average EDSS was 1.5 and
nobody was on any disease-modifying therapy, although most went on
treatment later. During the 5+ years, 18 did not progress but 13 did,
and these had an average EDSS of 4.5. A higher percentage of women
vs. men progressed, but otherwise the characteristics of both groups
were the same. The researchers looked at the baseline MRIs to see if
any of the measurements could predict who would go on to progress.
None of the usual MRI measurements (Gd+ lesions, T1 and T2 lesion
volumes, brain volume) differed between the progressors and
non-progressors, but whole brain magnetic transfer resonance (MTR) did
distinguish between the groups. However, MTR did not decrease over
time in either group, which is something the researchers are trying to
understand. (T2 lesion volume did decline faster in the progressing
group.)

An audience member noted that while these results had to do with brain
scans, EDSS reflects gait which is more affected by the spinal cord.
Dr. Richert replied that maybe what we see in the brain also reflects
what is happening in the spinal cord.

--

Evaluation of MS lesions using gradient echo plural contrast
imaging (Pascal Sati)

GEPCI is a new MRI technique that lets you get T1 and T2 data at the
same time (or something like that), resulting in faster scanning. It
captures almost all the lesions that a gold standard T1 or T2 detects,
and it also can show heterogeneity in normal appearing white matter
and gives a better gray/white matter contrast.

--

Relation between BBB leakage as expressed by Gadofluorine
M-enhanced MRI and infiltration of macrophages in EAE (Guido Stoll)

Gadofluorine-M (Gf-M) is an experimental contrast agent that is
dramatically more sensitive than gadolinium and can enhance lesions
not seen with Gd. Researchers used Gf-M to investigate the
relationship between blood-brain barrier disruption and acute
inflammation. They administered EAE mice with Gf-M (to detect
blood-brain barrier breakdown and cellular infiltration) and USPIOs
(to detect the entry of macrophages into the brain). Interestingly,
Gf-M and USPIO each labeled around 60-70 lesions, but only 4 of these
lesions were detected with both markers, meaning that the process of
macrophages entering the brain and the process of BBB breakdown and
cellular infiltration are largely separate. Macrophages don't need
BBB leakage to enter the brain, but perhaps they cause it after
they've gotten in.

* I give this presentation a star because it points to the potential
of new techniques to give us a much better understanding of what
happens when in CNS tissue affected by MS. I hope human studies
follow soon.

--

*** Satellite Symposium -- Researching the Potential for a New
Treatment Paradigm: Alemtuzumab in MS (Sponsored by Bayer HealthCare
and Genzyme) *** (Hollie)

At last year's ECTRIMS, there was a lot of exciting data about
alemtuzumab (Campath). Phase 3 studies are now underway so this was
more of an interim update to keep us all interested in the drug.

Mechanism of action (Joanne Jones)

Dr. Jones presented some research on the effects alemtuzumab may have
at a cellular level. The drug depletes both T and B cells; the B
cells that return are mostly naive cells and the T cells are mostly
memory/regulatory cells. Past studies have shown that disability
continues to improve up to three years after treatment ends,
suggesting that the cells that come back secrete neurotrophic
factors. So a series of experiments was conducted to see how cells
behave after exposure to the drug.

One experiment found that T cells (but not B cells or monocytes)
exposed to alemtuzumab increased their production of BDNF
(brain-derived neurotrophic factor) and decreased their production of
IGF-1 (insulin-like growth factor 1). Another experiment exposed
cultured rat embryo neurons to factors secreted by cells exposed to
alemtuzumab and found that neuronal survival was enhanced. (Survival
decreased when the neurons were exposed to cells obtained during
relapses.) A similar experiment found that OPC survival and
maturation was also enhanced by factors secreted by
alemtuzumab-cultured cells.

--

The other two talks, given by Krzysztof Selmaj and Edward Fox,
rehashed previous trial data and presented an overview of current
trials. An important bit of good news is that no new cases of ITP
(idiopathic thrombocytopenic purpura) have been reported in the
ongoing trials.

--

***Parallel session 7 -- Emerging Therapies *** (Hollie)

Treatments that target macrophages and microglia (Samia Khoury)

This was another overview talk, but at least it covered ground that
isn't discussed very often. Microglia are associated with axonal
damage, even in non-lesional areas. They may also inhibit
neurogenesis via release of inflammatory cytokines, and in animal
models, scientists have found activated microglia contacting stem cells
in the subventricular zone, and this contact may limit survival of
these stem cells. So inhibiting microglia and their relatives
macrophages may be a useful approach. There are lots of factors that
may accomplish this, including dexamethasone, vitamins E, D3 and A,
endocannabinoids, PPAR-gamma, CD200, and minocycline. Fortunately,
chronic microglia activation is found in chronic EAE, so there is an
animal model for doing some initial testing of these various factors.

Alemtuzumab significantly increases the proportion of clinically
disease-free patients with RRMS compared to subcutaneous IFN-beta 1a;
results from a phase 2 study (Krzysztof Selmaj)

This data comes from the CAMMS223 study. Compared with IFN-b,
alemtuzumab reduced cumulative relapses over 36 months by 74% and time
to sustained accumulation of disease by 71%. EDSS scores decreased on
average by 0.39 points in the alemtuzumab arm vs. increasing by 0.38
points in the IFN-b arm. (I think this data has been presented
already but I am reporting it here too just in case.)

Dr. Selmaj then presented new data showing that 80% of alemtuzumab
subjects remained relapse-free at 36 months vs. 50% of IFN-b subjects.
Percentages of subjects free from sustained accumulation of disability
were 86% vs. 67%, respectively. (Disability had to be sustained for 3
months to be counted.)

--

TERMS (Tovaxin for Early Relapsing MS) phase 2b
placbo-controlled trial of autologous T-cell vaccination in patients
with CIS or RRMS (Edward Fox)

Tovaxin is not a drug per se but a treatment involving culturing and
reinjecting a person's own T cells. The protocol involves drawing a
subject's blood, selecting T cells reactive for myelin proteins,
developing them into cell lines, freezing them, thawing them,
activating and expanding them, irradiating them so they can no longer
expand, and then reinjecting them into the subject. These steps are
performed five times in six months and the idea is to suppress
existing autoimmune T cells.

The TERMS trial included 100 people on the Tovaxin arm and 50 on
placebo. There was no significant difference between the two arms
with respect to the primary endpoint which was cumulative number of
Gd+ lesions. Dr. Fox suggested that the fact that the Tovaxin group
had a higher number of Gd+ lesions at baseline may have had something
to do with this. The Tovaxin group had a lower relapse rate but this
was not statistically significant. There were no major safety issues,
just mild injection site reactions. Dr. Fox said the study team is
now poring through the immunological and other data to see whether
there is reason to think this protocol would work better in a
particular type of MS subject.

--

Safety, phase I/II study with intrathecal and intravenous
injections of mesenchymal stem cells in patients with MS and ALS
(Dimitrios Karussis)

Dr. Karussis presented preliminary results from a study where
mesenchymal stem cells extracted from a subject's bone marrow were
cultured and then injected back into the person intravenously and
intrathecally. The 15 MS subjects had pretty severe disease: mean age
35, mean disease duration 10 years, mean EDSS 6.7. Six months after
treatment, the MS subjects' EDSS scores had dropped to 5.9 and nobody
had experienced any new relapses. MRIs did not reveal anything
unusual to be concerned about. Fever and headache were the most
common adverse events. There were also ALS subjects and overall they
appeared to stabilize. Dr. Karussis said that these results call for
larger, controlled studies.

--

Treatment of PML unfolding during monotherapy with natalizumab
(Ralf Gold)

Dr. Gold noted that as of June 2008, 43,000 people had been treated
with natalizumab. He then went on to give an update on a German
patient who had recently developed PML. This patient had a previous
five-year history of azathioprine and also had taken IFN-b at
intervals. He went on natalizumab as a monotherapy and had been on it
for 14 months when he developed PML with symptoms of hemiparesis
and cognitive changes. He had an MRI and his CSF tested positive for
JCV. He then was treated with antivirals, as well as plasmapheresis
to remove the natalizumab. This patient had an initial improvement,
but then unfortunately had a severe immune reaction called IRIS
(immune reconstitution inflammatory syndrome) which is marked by an
extreme inflammatory reaction. His JCV levels in the CSF had been
going down, but then spiked back up, perhaps due to the release of
viral antigens due to oligo death resulting from the strong
inflammatory response. Dr. Gold said the patient was doing quite
poorly. He noted that the benefit/risk ratio of natalizumab still
appears to be positive, but that physicians treating patients with
this drug must be very vigilant.

--

***Hot Topic 6 -- Novel cytokine, chemokine, and adhesion molecules
*** (Hollie)

Novel adhesion molecules of the blood-brain barrier (Alexander Prat)

Dr. Prat gave an overview of his work looking for new adhesion
molecules to block using mechanisms that are more selective than
natalizumab. These adhesion molecules include ALCAM and ninjurin.
Also needing to be determined is which cells to block and which to let
in.

--

MS immunologic and clinical behavior in parasitic infections
(Jorge Correale)

Dr. Correale described how he noticed that some of his MS patients
were infected with helminths (parasitic worms) -- he was
tipped off by higher eosinophil counts in their blood. These patients
were infected with at least six different types of helminths
collectively, and each infection was mild and didn't need to be
treated. He noticed that in these patients, relapse rate, EDSS
changes and new MRI lesions were very low compared with his other
patients. He is now studying what immunological changes these
infections might confer that could account for these clinical
benefits. For instance, in his infected patients, immune cells
produce less IL-12 and IFN-gamma and more IL-10 and TGF-beta. FoxP3
cells have stronger suppressive ability, and B cells produce more
BDNF. The B cell response may be due to a higher expression of
toll-like receptor 2 on B cells from infected patients. He is now
trying to figure out exactly which antigens are responsible for these
effects; perhaps that could be turned into a treatment that doesn't
involve actually being infected with a parasite.

--

Notch1 signaling regulates remyelination in the adult CNS
(Gareth John)

A variety of proteins known to be involved in cellular development are
found to be expressed in MS lesions, such as Jagged, Notch, and HES.
Notch1 regulates and restricts OPC maturation and has been studied in
initial development but not as much in the adult CNS. Dr. John's team
created a genetic mouse model that does not express Notch1 and induced
demyelination in these mice with lysolecithin. The mutants had
accelerated remyelination and reduced oligo precursor cell
proliferation than non-mutated mice. He next wants to test this mouse
using a chronic demyelination model and is wondering whether the mice
will run out of oligo precursor cells.

--

***Satellite Symposium -- Discovering new pathways in MS (sponsored
by Biogen Idec and Elan) *** (Hollie)

Defining the pathway of a new oral therapy (Amit Bar-Or)

This talk had to do with a drug called BG-12 (aka oral fumarate) which
is used in psoriasis and is being tested in MS. BG-12 reduces the
frequency of activated macrophages in EAE and its presumed mechanism
of action involves activation of the Nrf2 antioxidant pathway. BG-12
unbinds Nrf2 from another molecule so that it can assist in the
cellular defense against stress. A phase 2 study was conducted using
this drug in MS; it included three treatment arms and a placebo arm.
The highest dose appeared to affect MRI outcomes and there was a trend
toward lower relapse rate. Adverse effects included flushing and
gastrointestinal problems but these declined over time.

Two phase 3 trials are now underway (Define and Confirm) which will run
for two years and will have a control arm (placebo or Copaxone).

--

Transforming discovery into care (Richard Rudick)

Dr. Rudick gave a rundown of the various trials Biogen Idec/Elan
are conducting:

* Daclizumab -- the CHOICE trial showed a benefit in conjunction with
IFN-beta; it will now be studied as a monotherapy
* CDP323 -- this is an oral alpha-4 integrin antagonist; three phase 1
studies did not identify any major safety issues; a phase 2 study is
ongoing
* Anti-LINGO -- LINGO-1 is expressed on OPCs and demyelinated axons;
LINGO-LINGO contact inhibits remyelination; blocking LINGO promotes
OPC differentiation and remyelination; an anti-LINGO-1 molecule has
been shown to promote remyelination in various animal models
(cuprizone, lysolechithin, and EAE)

--

Saturday 09/20/2008:

Last day!

***Parallel session 10: Late breaking news *** (Hollie)

Efficacy and safety of rituximab in patients with PPMS: results
of a randomized, double-blind, placebo-controlled, multicenter trial
(Kathleen Hawker)

This study wins the award for silliest drug trial acronym -- its name
is "OLYMPUS" which stands for something like "Overcoming Lengths,
Yearning to Master, PPMS." Anyway, it deserves respect at least as
one of the few attempts to explore treatment of PPMS. This was a
96-week trial that administered either four courses of rituximab or
placebo to people with PPMS. Primary endpoint was time to confirmed
progression. Mean participant age was 50, disease duration was 9
years, and there were equal numbers of males and females. 25% of the
subjects had Gd+ lesions at baseline.

The drug did have the expected rapid effect on B cell depletion.
However, it did not have a significant effect on progression, with 30%
of the treated group progressing vs. 38% of the placebo group. T2
lesion volume was significantly lower in the treated group but there
was no effect on brain atrophy. Except for infusion reactions, there
were no major adverse effect differences between the two groups.

While the study did not find a significant effect on progression
overall, there was a significant effect in subjects who were 50 years
old or younger and had Gd+ lesions. So perhaps this drug is worth
evaluating further in this particular subgroup.

--

Results from a phase III, 1-year, randomized, double-blind,
parallel-group, dose-comparison study with glatiramer acetate in RRMS
(Giancarlo Comi)

This study sought to answer the question of whether a higher dose of
Copaxone (40 mg) would be more effective than the current 20 mg dose.
It involved 1,155 subjects and evaluated relapse rate and MRI results.
There was no advantage to the higher dose in terms of relapses, and
only a slight advantage in terms of Gd+ lesions. So there is no
apparent benefit to taking a higher dose of Copaxone according to this
study.

--

Nordic trial of methylprednisolone as add-on therapy to IFN-beta
for the treatment of RRMS (Per Sorenson)

This study evaluated whether adding methylprednisolone to ongoing
IFN-beta treatment would provide additional benefits to people with
RRMS. Subjects already on IFN-b were randomized to placebo or to 200
mg of MP for five consecutive days every four weeks for 96 weeks. The
enrollment goal was 150 subjects but only 130 could be recruited.

There was a statistically significant reduction in annualized relapse
rate (the primary endpoint) in the MP group over the placebo group
(relapse rates were 0.22 vs. 0.59). 70% of the MP subjects were
relapse-free vs. 28% of the placebo subjects (also significant).
There was a trend toward reduced time to sustained disability and
change in MSFC. Differences in MRI results were also seen, some
significant and some not. There were more adverse events in the MP
group (e.g., infections, sleep disturbances, psychiatric symptoms). A
new study called MECOMBIN is testing add-on MP to new IFN-treated
subjects. Results will be available in early 2009.

An audience member asked whether, given the side effects and low
enthusiasm of participants, add-on MP therapy was actually feasible.
Dr. Sorenson responded that the MECOMBIN trial has more resources to
deal with these issues and is having higher retention.

--

VLA-4 antisense: an oligonucleotide targeting VLA-4 mRNA
(ATL1102) significantly reduces new active lesions in patients with
RRMS (Volker Limmroth)

ATL1102 binds to VLA-4 mRNA, preventing it from being translated into
VLA-4 protein molecules. It's an injectable drug -- not one of the
current cohort of oral drugs being tested in MS. A small, short,
placebo-controlled study (80 subjects, 16 weeks) evaluated its effect
on MRI lesions in RRMS subjects. Both endpoints (cumulative number of
new active lesions and cumulative change in lesion volume) were met.
Two subjects discontinued treatment due to thrombocytopenia,
leukopenia, and/or neutropenia but these resolved after treatment was
stopped. No sign of JCV reactivation was seen.

--

Retinal pathology in MS: systematic evaluation of a large
autopsy series (Ari Green)

The retina contans specialized neurons that process light and
electrical signals. Dr. Green investigated whether the retina was
affected in people with MS. He examined 92 autopsy subjects (82 MS,
10 other neurological disease controls) and found that damage to the
optic nerve, retina, and blood-retina barrier was more common and more
severe in the MS samples than had been previously appreciated.

--

Causal link between human herpesvirus-6 and central inflammatory
demyelination (Claude Genain)

The common marmoset is a primate that shares 85-90% of its genes in
common with humans, and the MHC class II region that is associated
with MS is similar in both species. Since HHV-6 has been associated
with MS and found in MS brain tissue, Dr. Genain decided to see what
effect this virus might have in marmosets. Marmosets infected with
HHV-6 type B did not seem to experience many adverse effects, but
those infected with type A virus had clinical symptoms of
demyelination, confirmed by tissue analysis. HHV-6A persisted and
replicated in lesions as well as in oligos in NAWM. HHV-6A also
induced apoptosis (cell death) in oligos. The infected marmosets' T
cells also showed reactivity to MOG, but this was a delayed reaction.
Dr. Genain believes the mechanism of this animal model involves
migration of HHV-6A to the CNS, persistence of the virus there, oligo
death, and then myelin reactivity.

--

***Plenary session 3: Past, present, and future of
neurorehabilitation in MS (Nora Fernandez-Liguori) *** (Hollie)

In this, the last session of the conference, Dr. Fernandez-Liguori
hit some of the highlights of MS rehabilitation. Way back in the
past, popular treatments included cold water baths, suspension
apparatuses, and the "vaporium" (a device into which you put a
paralyzed limb and then fill with hot water).

The 1990's brought helpful clinical studies demonstrating reductions
in disability and other sustained benefits of neurorehabilitation.

More recent developments include the ability to measure effects on
neuroplasticity via functional MRI; constraint-induced training; and
treadmill walking with support. Cognitive neurorehabilitation is
still in the early stages of development. The field needs more
personnel and greater availability of treatment for patients.
--

***Poster sessions *** (Hollie)

In addition to the talks, there were also two poster sessions, one on
Thursday and one on Friday. Here are some of the highlights that I
observed, mostly related to the causes of MS which is our focus area:

* P96: Cigarette smoking and sex ratio of MS -- Observed recent
increases in the female/male ratio of MS could be largely explained
by higher smoking rates in women

* P105: Infection with specific strains of EBV are a risk factor for
MS -- Analysis of the EBNA-1 gene of EBV found sequence differences
in MS subjects vs. controls; perhaps some strains confer a higher
risk of MS than others

* P160: EBV antibodies and MRI in MS: a case for gene-environment
interactions -- The presence of the gene HLA B7 was associated with
higher anti-EBV antibody levels, higher disability, and more
destructive MRI parameters, indicating a potential gene-environment
link in MS

* P551: Association between actinic damage, a biomarker of lifetime
sun exposure, and first clinical diagnosis of CNS demyelination: the
Ausimmune Study: CIS subjects had greater sun-related wrinkling on
the backs of their hands than matched controls, indicating that sun
exposure (and therefore maybe vitamin D) protects against
demyelination

* P573: An international case-control study of risk factors for MS --
A research team is implementing a standardized questionnaire in
several different countries (Norway, Italy, Sweden, Serbia, and
Canada) asking about various MS risk factors such as diet, smoking,
and vitamin D (of interest to us since our repository questionnaire
asks about similar factors)

* P584: Smoking as an independent risk factor for MS: considering
possible combined effects with the HLA DR15 genotype and anti-EBNA
antibody titers -- Another gene/environment study showing that
smoking increased the MS risk associated with EBV infection (HLA
DR15 was not involved in this interaction)

* P590: A potentiation of the adverse effect of HLA DR15 on the risk
of MS by low infant sibling exposure: a population based
case-control study -- And another gene/environment study showing
that being positive for HLA DR15 is even more of a risk factor for
MS in people who didn't have much contact with younger siblings in
the first six years of life

* P595: Monthly ambient sunlight, vitamin D, infections and relapse
rate in MS -- Relapse rates were correlated with UV radiation when
lagged 1.5 months, predicted serum vitamin D levels (no lag), and
upper respiratory tract infection rate (no lag).

* P745: Impaired hypothalamo-pituitary-adrenal axis activity in MS
patients -- The HPA axis, which is involved in the response to
stress, has been found to be altered in people with MS, and this
study supports that concept, finding HPA hyperactivity in MS
subjects.

* P748: EBV is associated with gray matter atrophy and lesion injury
in MS: Similar to P160 above, this study (by the same team) found
anti-EBV antibodies to be associated with gray matter damage in MS.

* P819: Myelinating oligodendrocytes in the adult human cortex and
cortical lesions of MS patients -- Signs of active myelination were
seen in cortical tissue samples of subjects without MS, suggesting
that myelin in the cortex is continually remodeled; these signs were
also seen in 66% of cortical MS lesions

* P830: Substantial pyramidal cell loss in the motor cortex of SPMS
cases with meningeal B-cell follicles: About half of SPMS subjects
have clusters of B cells in the tissue lining the outside of the
brain; presence of these follicles are associated with greater gray
matter atrophy, loss of large pyramidal neurons, and increased
microglial activity and density in the gray matter

There were over 900 posters so we only got to see a few. If you want
to browse the abstracts of these posters (or any of the presentations),
you can do so online at:
http://msmontreal.abstractcentral.com/planner

--

That was it for the conference! My flight didn't leave until the
evening so I spent a pleasant afternoon in Montreal visiting Old
Montreal and the giant underground shopping mall along Ste. Catherine
(along with approximately half of everyone else in Montreal).

My summary of the conference is:

* There is a lot of interest and activity in novel MS drugs. Some
will pan out and others won't, but in a few years there should be
several more options for people with MS.

* It was good to see results from a couple of PPMS studies and I
hope eventually at least *one* drug will be shown to be able to
benefit people with this disease.

* I enjoyed the session where neurologists discussed how they deal
with different issues. There are many gray areas in treating MS so it
was interesting to hear how these are dealt with in daily practice.

* Several imaging and pathology studies illustrated progress that is
being made in understanding how damage occurs in MS and what factors
may be preventing remyelination. I'd like to see much more of this
type of work being done.

* Last but not least, it was encouraging to finally see scientists
analyzing multiple factors at the same time to identify interactions
that influence risk or severity of MS. MS has been recognized as a
multifactorial disease for several years, so we should be looking for
combinations of factors that are associated with MS. Hopefully there
will be even more of this type of research at next year's ECTRIMS.