Art and Hollie's Notes From the 2008 AAN Meeting in Chicago

Art and Hollie's Notes From The 2008 AAN Meeting In Chicago

Each year Accelerated Cure Project attends the American Academy of Neurology

American Academy of Neurology meeting 4/14/07 - 4/20/07 Chicago, IL

This year the AAN was held in the Windy City. A short flight to a
similar climate. We had a booth this year (staffed by Kristin and
volunteers Noeli and Danica McClelland) and Hollie and Art attended
the MS talks and took notes.

This year we have noted the talks we especially liked or thought were
important. You can search for "Art Pick" or "Hollie Pick" to find
them. Our notes are below.

continued...

Mon 04/13:

Art and Kristin flew in from Boston on Sunday eve, grabbed a couple
of beers and retired for the night to our newly-renovated rooms at the
Essex Inn (which was reportedly half as expensive and much nicer than
the Hilton across the street).

We got up on Monday and made our way over to the convention
center. We grabbed our registration materials and carted our stuff
over to our booth on the exhibit hall floor. We set up our area with
no problems (I think this was a first) and then headed back to the
hotel to eagerly await the evening "Exhibit Hall Reception."

Afterward, we met up and had dinner with Hollie who had just flown
in.

Tue 04/14:

Art got to the conference early to meet with one of the docs from
Biogen Idec to get some questions answered about the design of the
BG-12 trial. He then wandered around and ran into various other docs
we have befriended over the years.

*** Art Pick

We also went to the poster sessions. One poster, reporting the results
of Bruce Cree of UCSF's Low Dose Naltrexone (LDN) study, was of
particular interest as we worked with the volunteers who raised funds
to make it happen. It was a short (8 weeks) and small (60 subjects)
study looking at quality of life in MS (all types). The results showed
significantly improved quality of life indices for mental health,
pain, and self-reported cognitive function as measured by the MSQLI.
No similar benefit was seen for physical quality of life.

This is important because it gives some credence to the use of LDN
and should lead to other studies. It also gives those trying to get
their docs to let them try LDN something to show in support of its
efficacy and safety in MS.

Other posters that were of interest throughout the conference
included:

• A poster presented by Jana Goins describing our MS
  Repository (thanks, Jana!)

• One presented by Lauren Puccio (our repository study
  coordinator at the MS Research Center of New York) –
  they have found JC or BK virus DNA in the plasma or CSF of 7
  of their 200 Tysabri recipients (fortunately, the DNA presence
  disappeared after Tysabri cessation, and nobody has developed
  any signs of PML)

• A poster presented by Ben Greenberg (our Johns Hopkins
  PI) and his Diogenix collaborators concerning biomarker work
  which we're helping to further through our repository

• Joshua Bacon presented results from a trial that showed
  improved memory, working memory, and processing speed in MS
  subjects after participation in a six-week cognitive rehab
  program

• U. Dalgas had a poster showing that resistance training
  can help reduce fatigue and depression in people with MS

There were probably lots of other interesting posters, but the rows
of posters were positioned so close together that at times there were
just solid people in the aisles and no way of getting through to see
anything. (Seriously, it was worse than a mosh pit!)

The Exhibit hall opened and we met with our volunteers who are
helping staff the booth. Art took a quick whirl round the hall to see
who was there and what they were hawking.

S02 MULTIPLE SCLEROSIS: CLINICAL TRIALS I (Art & Hollie)

2:00 P.M. S02.001 Statistical Analysis of Clinical Endpoints
in Studies of Disease- Modifying Therapies for Multiple
Sclerosis Gary Cutter, Maria Sormani, Amy Pace, Hao Zhang

Comparing results across MS clinical trials is difficult. We'd like
to be able to do it so that we can know if drug X is better than drug
Y when they weren't both used in the same trial. This difficulty comes
from variations in study design, e.g., the definition of what
constitutes a relapse can vary from trial to trial in the following
ways:

• how relapse is confirmed

• how long after onset the relapse
  is confirmed

• method of confirmation

• if subjects can be treated before
  relapse is confirmed

• duration required to consider it a
  relapse

• etc.

These researchers looked at published clinical trial data from 1960
to mid-2007. They found 200 applicable papers but only 79 had all the
data they needed to do the analysis.

By looking at the untreated groups in each study, they found that
the reported annualized relapse rates had dropped significantly since
the 1980's, most likely because criteria have become more stringent
(requiring the relapse to last 48 vs. 24 hours and requiring
neurologist confirmation, for example). Changes in the relapse rates
seen in a trial will affect the summary measures from which
conclusions are drawn, such as relative relapse reduction and number
needed to treat, so be very careful when comparing results across
studies!

2:15 P.M. S02.002 Natalizumab Utilization and Safety in
Patients with Relapsing Multiple Sclerosis: Updated Results from TOUCH
and TYGRIS Carmen Bozic, Glyn Belcher, Mariska Kooijmans-
Coutinho, Richard Kim, Robert Hyde, Frances Lynn, Michael Panzara

This was basically a status update on the use of Tysabri, as
tracked by the FDA-mandated TOUCH monitoring program and of the Biogen
Idec-run TYGRIS monitoring program.

Tysabri has been approved in 30 countries, and approximately 37,000
people have taken Tysabri. 9,900 have taken it for more than 1 year,
and 3,600 have taken it for more than 18 months. There have been no
new cases of PML found and none of the 396 people tested for JCV DNA
in their CSF have been positive. Five people whose plasma was tested
for JCV DNA were positive, but three of these weren't on Tysabri. The
sub-registry for patients who get pregnant while on Tysabri has
enrolled 36 women so far. Several of them have had healthy deliveries
already and the number of miscarriages was within the normal
range.

The percentage of people discontinuing use of the drug so far is
lower than typical rates for the ABCR drugs.

2:30 P.M. S02.003 The Safety of TYSABRI Re-Dosing and
Treatment (STRATA) Study Paul W. OConnor, Andrew D. Goodman,
Ludwig Kappos, Fred D. Lublin, Chris H. Polman, Richard Rudick,
Stephanie Jurgensen, Nisha Lucas, Ayad Abdul-Ahad, Michael Panzara

This study looked at what happened to the subjects who were in the
initial Tysabri studies who had to stop due to the FDA shutdown and
then restarted after Tysabri came back 1.5 years later.

They found that returning to Tysabri, even after being on another
drug, appears safe. They also found that those who had only had 1 or 2
previous doses had a greater chance of having an infusion reaction
when they restarted.

Other statistics they presented were that 5% of patients had
infusion reactions and less than 1% had hypersensitivity reactions.
These reactions were most likely to occur on the second dosing (24% of
reactions). 6 of 1089 people had JC virus (the cause of PML) DNA in
their plasma, but no cases of PML.

2:45 P.M. S02.004 The Efficacy of Cladribine in
Relapsing-Remitting Multiple Sclerosis: Magnetic Resonance Imaging
Data from a Randomized, Double-Blind, Placebo-Controlled, 18-Month,
Phase II Trial Jack C. Sipe, Jason Gardner, Ernest Beutler

This presentation was a bit odd, given that the data being
presented was 10 years old. It was a reanalysis of MRI data from a
clinical trial but no explanation was given why such old data would be
presented.

This study, called SCRIPPS-C, gave 49 subjects either placebo or 6
courses of subcutaneous cladribine monthly. Each course consisted of 5
daily shots. They found that it reduced Gd+ T1 and T2 lesions, 98%
reduction in lesion volume at 18 months, 32% relapse reduction, and
few adverse events. They mentioned that there is an oral formulation
in trials currently. It would have been more interesting to hear about
that.

3:00 P.M. S02.005 A Phase I/II Dose Escalation Trial of Oral
Vitamin D3 with Calcium Supplementation in Patients with Multiple
Sclerosis Jodie M. Burton, Samantha Kimball, Reinhold Vieth,
Amit Bar-Or, Hans- Michael Dosch, Louise Thibault, Sally Kilborn,
Cheryl DSouza, Melanie Ursell, Paul OConnor

*** Art Pick

*** Hollie Pick

There is increasing evidence that Vit D3 has protective effects from
MS. But does it help people who already have MS? This study looked at
how much Vit D3 you can give someone safely and a little bit at how it
might affect MS.

The trial was 12 months and had 50 subjects. Half received a dose
that escalated from 4,000 IU to 40,000 IU over a six month period and
then dropped back to 10,000 IU daily. The other half were on a control
arm that received 4,000 IU throughout the study. Subjects were
supplemented with calcium phosphate 1200mg/day as there is evidence of
hypocalcemia from high Vit D3 levels. There was no overall EDSS
worsening and relapses occurred in only 16% of those on Vit D3 vs. 40%
of those on placebo. Calcium levels remained steady. In the
escalating group, the serum 25(OH)D levels did go above the current
“toxic” level, but no harmful effects were reported. The
speaker noted that the subjects whose peak vitamin D doses occurred in
the winter were more likely to have stable or improved EDSS scores at
the end of the trial. She also noted that in future studies, she would
recommend using a dose of 10,000 UI/day since this is similar to what
is received via sunlight at the equator.

3:15 P.M. S02.006 Immunogenicity, Tolerability and Patient
Disposition in a Randomized, Assessor-Blinded, Multicenter Study of
Interferon Beta-1a and Glatiramer Acetate in Patients with Relapsing-
Remitting Multiple Sclerosis: Results from the REGARD Study
Patricia K. Coyle, Frederik Barkhof, Peter Chang, Douglas R. Jeffery,
Dan D. Mikol, Steven Schwid, Bettina Stubinski, Bernard
M. J. Uitdehaag

This study (96 weeks, 758 subjects)
compared high-dose IFN-beta (Rebif) with glatiramer acetate
(Copaxone). There was no difference between the two arms in the
primary outcome which was time to first relapse. Results from a
secondary imaging measure favored Rebif. Adverse events were similar
in both groups. 33% of Rebif recipients developed neutralizing
antibodies at some time during the trial; however, 19% reverted. Nabs
didn't seem to affect clinical outcome but it did significantly affect
T1 Gd+ lesions. 98% of the GA recipients developed binding antibodies
but apparently these didn't prevent the drug from being effective in
at least some people.

S12 MULTIPLE SCLEROSIS: CLINICAL TRIALS II (Art & Hollie)

3:45 P.M. Presentation of the John Dystel Prize for Multiple
Sclerosis Research Recipient: Stephen Hauser, MD, San
Francisco, CA

Steve Hauser of UCSF was presented with the Dystel prize (a sort of
life-time achievement award). He gave a talk on some of his past work
in immunology and genetics of MS. He also made some predictions about
things we will understand by the year 2013:

• All the common MS risk variants

• What percentage of the disease is due to rare variants

• The role of copy number variants

• Why some ethnicities are more resistant to MS

• The role of epigenetics and methylation

• How gene transcriptional profiles relate to the disease
  phenotype and prognosis

• Clinically useful biomarkers

• Patterns of genes in the context of functional pathways

Looks like our work for the next five years is cut out for us!

4:15 P.M. S12.003 Safety and Immunogenicity of a New
Formulation of Interferon Beta-1a (Rebif New Formulation) in a Phase
IIIb Study in Patients with Relapsing Multiple Sclerosis: 96-Week
Results James Simsarian, Olga Barbarash, Florence
Casset-Semanaz, Gavin Giovannoni, John King, Luanne Metz, Gabriel
Pardo, Per Soelberg Sorensen, Bettina Stubinski

This was a presentation of the data that allowed Rebif to bring a
new formulation on the market. Its purpose was to improve tolerability
and immunogenicity. Neutralizing antibody levels were significantly
lower (17% down from 27%) than the old formulation. They had a
similar percentage of drop-outs due to tolerability in this study as
in the study from the old version, so it isn't clear how they
concluded that it was more tolerable.

4:30 P.M. S12.004 A Phase I, Open-Label, Multicenter Study To
Evaluate the Safety and Activity of Rituximab in Adults with
Relapsing-Remitting Multiple Sclerosis (RRMS): 72 Week Results
Amit Bar-Or, Peter Calabresi, Douglas Arnold, Clyde Markowitz, Stuart
Shafer, Lloyd Kasper, Emmanuelle Waubant, Suzanne Gazda, Robert Fox,
Neena Sarkar, Michael Panzara, Craig Smith

This talk reported the continuing results of a study we've written
up from previous conferences. 22 subjects have now reached the 72 week
point. They were given 2 infusions 2 weeks apart, then again at 6
months. Adverse events included headache, chills, hypotension, and
throat irritation. CD19+ B-cells (the drug's target) are wiped out
completely for 6 months. Gd+ lesions went from an average of 1.25 to 0
and relapses went from 1.3/yr average to 0.23. 81% of subjects were
relapse free after 72 weeks.

These results are consistent with was reported previously, but it
is good to see that the effects continue on for this long.

4:45 P.M. S12.005 Oral FTY720 (Fingolimod) in Patients with
Relapsing Multiple Sclerosis. 3-Year Extension Shows Sustained Low
Relapse Rate and MRI Activity Giancarlo Comi, Paul OConnor,
Xavier Montalban, Jack Antel, Ernst-Wilhelm Radu, Ana De Vera, Harald
Pohlmann, Ludwig Kappos

This is a continuation of a study reported on at previous
conferences. At 36 months 89% of the subjects were Gd+ lesion free,
70% T2 lesion free, and 70% relapse free. A phase 3 trial is ongoing.

Party Time

That evening we went out to dinner at
Morton's Steak House with a large group of Johns Hopkins employees,
students, alums, and friends.

Wed 04/15:

S22 MULTIPLE SCLEROSIS: CLINICAL TRIALS III (Art)

2:00 P.M. S22.001 Treatment of MS Patients with Selective
PDE-4 Inhibitor Rolipram Inhibits Th1/Th17 T Cell Responses, but Fails
To Inhibit Brain Inflammatory Activity Bibiana Bielekova,
Robert Orlowski, Thomas Howard, Nancy Richert, Jayne Martin, Jehad
Edwan, Joan Ohayon, Henry McFarland, Roland Martin

This trial of Rolipram was stopped prematurely by the Data Safety
Monitoring Board as it seemed to increase contrast enhancing lesions
even though it inhibited Th1 cytokine production. Data was presented
on the immunological assays that were done.

2:15 P.M. S22.002 Pharmacokinetics and Pharmacodynamics of
Rituximab in Adults with Relapsing Remitting Multiple Sclerosis (RRMS)
in a 48-Week Phase II Placebo-Controlled, Multicenter Trial
Amit Bar-Or, Emmanuelle Waubant, Song Ren, Neena Sarkar, Craig Smith

This was a presentation of more data (PK/PD) from the trial that
was presented yesterday. The data were not of general interest in my
opinion so I shall spare you the details (and me the pain of writing
them all down).

2:30 P.M. S22.003 Results from a Phase 2b Trial of a Myelin
Basic Protein Encoding DNA Vaccine for Relapsing Multiple
Sclerosis Hideki Garren, William Robinson, Eva
Krasulová, Eva Havrdova, Congor Nadj, Krzysztof Selmaj, Jacek
Losy, Ilinka Nadj, Ernst-Wilhelm Radu, Brian A. Kidd, Jill Gianettoni,
Karen Tersini, Paul J. Utz, Frank Valone, Lawrence Steinman

This is the drug also known as BHT-309 from Bay Hill Therapeutics.
This presentation looked at data from the subset of 80 subjects who
provided CSF. They found that subjects who had higher IgG levels in
their CSF had a greater reduction of Gd+ lesions and greater reduction
in relapse rates. The safety profile was the same as placebo. The
lower dose worked better than the higher. There's a Phase 2b trial
scheduled for Q408 where they will screen subjects for higher IgG
levels for entrance.

2:45 P.M. S22.004 Comparison of Two Therapeutic Strategies in
Aggressive Relapsing-Remitting MS: Mitoxantrone as Induction for 6
Months Followed by Interferon- b-1b Versus Interferon-b-1b. A 3-Year
Randomized Trial Emmanuelle Le Page, Giancarlo Comi, Massimo
Filippi, Gilles Edan, French-Italian Mitoxantrone- Interferon-beta
Trial Group

*** Art Pick

In this study they compared administering mitoxantrone (mitox) and
methylprednisone (MP) for 6 months, then a 3 month break, then
Betaseron to just taking Betaseron for the whole time. 55 started on
mitox+MP and 54 on IFN. 33 finished mitox+MP and 28 finished IFN. 5
mitox+MP had their disability worsen vs. 14 for IFN alone. Mitox+MP
group had an average .44 annualized relapse rate vs. 1.14 for IFN
alone. Mitox+MP delayed time to first relapse and 29 mitox+MP were
relapse free at the end of the study vs. 15 on IFN alone. The mitox+MP
group had a higher incidence of adverse events.

3:00 P.M. S22.005 Plasma Exchange Accelerates the Decline of
Serum Natalizumab Concentration in Patients with Multiple Sclerosis:
Results of the Natalizumab PLEX Study
Bhupendra Khatri,
Robert Fox, Anna P. Koo, Frances Lynn, Petra Duda, Stephanie
Jurgensen, Michael Panzara, Gavin Giovannoni

Rapid immune system reconstitution is known to improve the outcomes
of people who develop PML. In the past, 2 MS patients on Tysabri
contracted PML. Tysabri takes up to 3 months to flush from the
system. Having a way to flush Tysabri faster would be beneficial
should others contract PML.

This study looked at the effect of 3 plasma exchange (PLEX)
sessions 14 days after having at least 3 Tysabri infusions. 12
subjects at 2 sites who are on Tysabri agreed to enter this study.
They found that there was ~95% reduction in serum concentration of
Tysabri, although the alpha4-integrin saturation was not affected very
much (that's the molecule Tysabri binds to). The serum concentration
needs to get lower than it did in most of the subjects in this
study. Models suggest that 5 PLEX sessions are needed to get the serum
concentration levels low enough to benefit 95% of patients. But this
does look like a promising way to flush Tysabri if others contract
PML.

3:15 P.M. S22.006 Alemtuzumab Compared with Subcutaneous
High-Dose IFNB-1a in Treatment-Naive Relapsing-Remitting Multiple
Sclerosis: Primary Efficacy Outcomes of CAMMS223 at 3 Years
Alasdair Coles, CAMMS 223 Study Group

*** Art Pick

This is the long term data of the previously reported CAMPATH
study. People were enrolled who had early MS (<3 years, EDSS <=
3.0) and were put on a 2 or 3 course regimen of CAMPATH and compared
to subjects on Rebif. Keep in mind the results described are compared
to Rebif and not to placebo.

Safety profile showed CAMPATH having slightly more adverse events,
mostly due to infusion related reactions and more infections. Two
people died in the trial (1 due to ITP and 1 unrelated). 25% of the
subjects got thyroid problems, all of which were treated and
resolved. 5 additional cases of ITP were identified and treated to
resolution.

Results showed 74% reduction (again, compared to Rebif) in
relapses, 71% reduction in subjects sustaining disability and an
*improvement* in EDSS (-.39 average vs. +.38 for Rebif). Two phase 3
studies are currently enrolling.

S27 MULTIPLE SCLEROSIS: IMMUNOLOGY I (Hollie)

2:00 P.M. S27.001 Autoimmune Myelopathy Associated with
CRMP-5-IgG Mark Keegan, Sean Pittock, Vanda Lennon

This speaker described a form of autoimmune myelopathy that is
usually progressive, is marked by antibodies to CRMP-5, and is often
found coexistent with small-cell carcinoma.

2:15 P.M. S27.002 Functional Effects of NMO- IgG on Blood
Brain Barrier Permeability, Astrocyte Injury and Granulocyte
Recruitment Thierry Vincent, Philippe Saikali, Romain Cayrol,
Alexandro Roth, Amit Bar-Or, Alexandre Prat, Jack Antel

Antibodies to aquaporin-4 (aka NMO IgG) are often found in the
serum of people with neuromyelitis optica, and aquaporin-4 is highly
expressed in astrocytes indicating that this cell is particularly
affected in this disease. The research described in this presentation
sought to understand what specific effect NMO IgG has on astrocytes.
The team used a culture system of human astrocytes and endothelial
cells to build a model of the blood-brain barrier and exposed it to
NMO IgG to see what would happen. The barrier became more permeable,
AQP-4 was lost from the astrocytes' endfeet processes, and mechanisms
such as natural killer cell degranulation and antibody-dependent
cellular cytotoxicity resulted in astrocyte death.

2:30 P.M. S27.003 Neuromyelitis Optica Brain Lesions Are
Pathologically Identical to Optico-Spinal Lesions Shanu
Roemer, Joseph Parisi, Wolfgang Bruck, Hans Lassmann, Margaret Esiri,
Sean Pittock, Vanda Lennon, Claudia Lucchinetti

60% of people with NMO have brain lesions as well as lesions in the
spinal cord and optic nerve. This team conducted a brain tissue
analysis study to characterize these lesions – are they like
optico-spinal NMO lesions or are they more like MS or ADEM lesions?
(That's a good question!) It appears they are similar to the
optico-spinal lesions in terms of presence of eosinophils and
complement and loss of AQP-4. They are also similar to the
optico-spinal lesions in that some lesions are
destructive/demyelinating and some are not. However, brain lesions in
NMO are distinct from MS lesions and ADEM. For instance, AQP-4 is
still present in MS lesions. These results were the same in both
NMO-IgG-positive and -negative NMO subjects.

2:45 P.M. S27.004 B Cell Depletion in Multiple Sclerosis
Results in Diminished Th1 and ThIL-17 Responses by CD4 and CD8 T
Cells Boli Fan, Lama Fawaz, Aja Rieger, Ichiro Nakashima,
Farzaneh Jalili, Gregory Cosentino, Amit Bar-Or

In MS subjects, B cells are deficient in their production of IL-10
but produce more TNF-a and LTA in pro-inflammatory environments.
Rituximab, which is undergoing clinical trials in MS, depletes a
person's B cells, which reduces proliferation of CD4 and CD8 T cells.
The B cell population eventually builds back up – but is this
new population the same as before or different? This study compared
blood samples taken before and after rituximab treatment and found
that during reconstitution, a higher proportion of naïve vs.
memory B cells are created. Perhaps depletion removes more
pro-inflammatory memory B cells and thus dampens the inflammatory T
cell response. The reconstituted B cells are less inflammatory, more
regulatory in nature. The next question to be answered is how does
removal of B cells in the peripheral bloodstream (outside the brain)
lead to decreased disease activity inside the central nervous
system.

3:00 P.M. S27.005 Plasma Exchange Augments Leukocyte
Transmigration across an In Vitro Blood-Brain Barrier in
Natalizumab-Treated Patients with Multiple Sclerosis Robert
Fox, Shumei Man, Barbara Tucky, Jar-Chi Lee, Anna P. Koo, Gavin
Giovannoni, Bhupendra Khatri, Susan Goelz, Richard Ransohoff

This is a sister presentation to the PLEX study described above.
Blood cells taken from natalizumab recipients before and after PLEX
were put in a culture system that simulated the blood-brain barrier.
The post-PLEX blood cells did indeed have a higher rate of migration
across the barrier than the pre-PLEX cells, indicating that PLEX would
help to reconstitute the immune system in the brain if needed in
natalizumab recipients.

3:15 P.M. S27.006 Coexisting Autoimmune Channelopathies:
Neuromyelitis Optica (NMO) with Myasthenia Gravis (MG) Koon Ho
Chan, Sean Pittock, Vanda Lennon

This presentation described 16 people who had both NMO and
myasthenia gravis. Fifteen of them developed MG first. The NMO
symptoms (e.g., paraplegia and blindness) accounted for most of the
disability experienced by these people. The co-existence of these two
diseases suggest that MG and NMO may share some risk factor(s) in
common.

S32 MULTIPLE SCLEROSIS: IMAGING I (Art)

3:45 P.M. S32.001 Grey Matter and White Matter Volumes at
20-Year Follow-Up of a MS and CIS Cohort Seen from Onset
Leonora K. Fisniku, Jonathan Jackson, Declan Chard, Daniel Altmann,
Alan Thompson, David H. Miller

This study followed 73 people with CIS and MS and 25 controls for
20 years. They found that grey matter (GM) atrophy was greater than
white matter (WM) atrophy. GM atrophy correlated with disability and
lesion load while WM atrophy did not. They did not look at spinal
cords, only brains.

4:00 P.M. S32.002 A 4-Year Longitudinal Study of Gray Matter
Atrophy in Multiple Sclerosis Patients Elizabeth Fisher,
Jar-Chi Lee, Kunio Nakamura, Richard Rudick

*** Art Pick

This study found that atrophy rates increase with disease progression
(like the last study). WM atrophy happened at a fairly constant rate
over the progression of MS (CIS->RRMS->SPMS) at about 3X the
rate of controls. GM atrophy, however, accelerates with disease
progression going from about 3X to 8X to 14X the rate of
controls. They found a moderate correlation between GM atrophy and
EDSS. WM atrophy correlated with GM atrophy in RRMS, but not in
SPMS. They conclude that MS appears to be a predominantly GM disease.

This has big implications for how drugs are developed and approved
given our previous bias that it was strictly a WM disease.

4:15 P.M. S32.003 MRI Abnormalities in the Optic Tract in
Multiple Sclerosis: Association with Visual Dysfunction and Retinal
Thinning Hormuzdiyar H. Dasenbrock, Eliza Gordon-Lipkin, Seth
Smith, Peter Calabresi, Daniel Reich

This study reports correlations between imaged abnormalities of the
optic cord tract and visual dysfunction in MS. While the results had
statistical significance, the graphs demonstrating the trend line
looked like an arrow flying through a cloud and didn't appear that
convincing.

4:30 P.M. S32.004 Cognitive Impairment and Multiple
Sclerosis: The Role of Microscopic and Macroscopic White Matter
Pathology Giuseppe Bomboi, Vasiliki N. Ikonomidou, Stefano
Pellegrini, Susan K. Stern, Antonio Gallo, Iordanis E. Evangelou,
Jhalak Agarwal, Joan Ohayon, Fredric Cantor, Mary Ehrmantraut, Robert
Kane, Henry McFarland, Francesca Bagnato

This study concluded that non-lesion WM damage correlates with some
cognitive dysfunctions in MS.

4:45 P.M. S32.005 Recovery of Tumefactive Demyelinating
Lesions in a Multiple Sclerosis Patient as Evidenced by Magnetization
Transfer Imaging Vasiliki N. Ikonomidou, Joan M. Ohayon,
Natalie E. Cook, Nancy Richert, Bibiana Bielekova, Henry McFarland,
Francesca Bagnato

OK, I admit that I took a bio-break at this point and didn't go
back in to the talk. Sue me.

S35 MULTIPLE SCLEROSIS: IMMUNOLOGY II (Hollie)

3:45 P.M. S35.001 The Dramatic Abrogation of Inflammatory
Disease Activity in MS Patients Treated with Immune Ablation and
Autologous Haematopoetic Stem-Cell Transplantation (AHSCT) Is
Associated with Significant Decreases in ThIL- 17, but Not in Th1
Responses Tarik Touil, Denis Gaucher, Hania Kebir, Joumana
Zeidan, Ho Jin Kim, Rachel Corsini, Dominique Gauchat, Martin Duddy,
Farzaneh Jalili, Jacqueline Chen, Douglas S. Arnold, Catherine
Hilliker, Guylaine Theoret, Marjorie Bowman, Mark S. Freedman, Harold
Atkins, Remi Cheynier, Nathalie Arbour, Alexandre Prat, Rafick Sekaly,
Amit Bar-Or

This study asked a question that was similar to the Rituximab one
above (S27.004) – when you wipe out the immune system of a
person with MS and then allow it to repopulate, what kinds of cells
are in the new population? In the subjects in this study, immune
system depletion and reconstitution was achieved with immune ablation
and haematopoetic stem cell transplantation (AHSCT). The Th1/Th2
profile of these subjects didn't change, but production of the
pro-inflammatory cytokine IL-17 was reduced after the procedure.
There were also more CD56-high natural killer cells present which are
immunoregulatory (as opposed to CD56-low NK cells which are
cytotoxic).

4:00 P.M. S35.002 Atorvastatin Treatment of CNS Autoimmune
Disease Acts through Suppression of Proinflammatory Th1/Th17 Responses
and Does Not Require STAT6-Mediated Th2 Differentiation or Promote
Development of CD4+CD25+FoxP3+ Regulatory T Cells Martin
S. Weber, Thomas E. Prodhomme, Sawsan Youssef, Cynthia Rundle, Shannon
Dunn, Lawrence Steinman, Scott Zamvil

I think the extremely long title of this presentation pretty much
sums it up! I'll just note that this study was performed in mice and
was conducted to find out why statins prevent/reverse EAE – the
upshot is that statins inhibit proliferation and differentiation of
both Th1 and Th2 cells as opposed to promoting the development of
regulatory T cells.

4:15 P.M. S35.003 Simvastatin Inhibits Myelin Repair in the
Cuprizone Model Veronique E. Miron, Simone P. Zehntner,
Timothy E. Kennedy, Barry J. Bedell, Jack Antel

These researchers used an animal model of demyelination and
remyelination that involves feeding mice a toxin called Cuprizone.
They found that injection of simvastatin either during the
oligodendrocyte recruitment phase or the remyelination phase resulted
in lower levels of remyelination. Different numbers of oligo
precursors were seen in the brains of mice that received statins vs.
those that did not, so perhaps the statins interfered with the oligo
maturation process?

4:30 P.M. S35.004 Conversion of Naïve Effector CD4+
Cells to Regulatory T Cells Ex Vivo: A New Immunotherapy for Treatment
of Relapsing Multiple Sclerosis? Jacqueline Channon, Sandie
Mennechet, Xiaosong Wang, Alan Bergeron, Micah Benson, Randolph
Noelle, John DeLong, Kathleen Smith, Lloyd Kasper

Dr. Channon presented a potential MS therapy whereby a person's
naïve T cells would be extracted, converted to FoxP3-expressing
regulatory cells, expanded in culture, and then reinjected into the
person to suppress inflammation. Early indications are that enough
cells could be produced in culture to make this approach feasible.
The team will be trying this next in mice with a humanized immune
system.

4:45 P.M. S35.005 Different Subsets of CD8+ Regulatory T
Cells Modulate the Immune Response during the Course of Multiple
Sclerosis Jorge Correale, Andrés M. Villa

There is a class of CD8+ T cells that express CD25 as well as FoxP3
– these cells can inhibit T cell proliferation through
cell-to-cell contact and they also produce anti-inflammatory
cytokines. These cells are less abundant in people who are having an
MS relapse compared with remitting MS or controls, which makes sense,
I guess.

At the end of the day, Kristin insisted that we go to the Original
Rock and Roll McDonalds she saw when she drove to the hotel. It's a
huge two-story McD's that played irritating Jazz music instead of rock
and roll (go figure) and had funky booths and a dessert bar upstairs.

Thu 04/16:

S42 MULTIPLE SCLEROSIS: GENETICS AND PATHOGENESIS (Art)

1:30 P.M. S42.001 Alleles in the OLIG Gene Locus Affect the
Rate of Brain Atrophy in Multiple Sclerosis Brian Healy,
Charles Guttmann, Mehul Sampat, Howard Weiner, David Hafler, Philip De
Jager

The idea of this study was to see if there were genetic markers
that correlated with brain atrophy in MS. The 4 known MS associated
gene loci did not show an association with brain parenchymal fraction
(BPF), a measure of brain atrophy. A larger SNP scan found no alleles
that correlated with BPF. The models used to do this association
study appeared to be good, so they are working on a follow-on study.

1:45 P.M. S42.002 Distribution of Acute Active Plaques and
Low-Grade Active Demyelination in Progressive Multiple Sclerosis
(MS) Stephan Bramow, Per Sorensen, Hans Lassmann, Nils
Koch-Henriksen, Henning Laursen

This study looked at tissue from 17 SPMS and 4 PPMS subjects. They
cataloged plaques described as: active, slowly expanding, and
inactive. The active and slowly expanding plaques were found more
often than expected for progressive MS. All regions of the brain were
affected. They also found inflammatory demyelination in long duration
MS, which was a bit of surprise.

2:00 P.M. S42.003 Mitochondrial Mutations in Pediatric
Clinically Isolated Demyelinating Syndromes (CIS) Sunita
Venkateswaran, Mary Sacchetti, Douglas Arnold, Dessa Sadovnick, Julia
Kennedy, Donald Gagne, Brenda Banwell, Amit Bar- Or, David Simon

*** Art Pick

This study was of particular interest to us as it used samples from
the Accelerated Cure Project repository. This was the first AAN where
the results of our work were becoming visible. We had this study that
used our samples, a poster presented by Jana of Johns Hopkins on the
repository as a whole, a poster by Ben of Johns Hopkins on a project
we are collaborating on, and a poster on the LDN study we helped
orchestrate funding for.

This study looked at 116 pediatric CIS cases, 346 MS (from our
repository), and 213 controls (also from our repository). They looked
at mitochondrial DNA (mtDNA) mutations. They found no LHON mutations
(which cause a well known mtDNA disease). 6% of the ped-CIS cases had
a mtDNA mutation compared to 1.5% of the MS and .5% of the control
group. The Haplotype J group (a particular set of genetic markers)
was higher in the MS group than controls.

This study allowed them to understand how big of a population they
need to look at and we will work with them on doing the bigger study.
It was also nice to see that two of the researchers who got up to ask
questions were also using our samples (for other genetic studies).

2:15 P.M. S42.004 Allelic Variation Telomeric to DRB5
Influences Multiple Sclerosis Susceptibility Independently of HLA-DRB1
in African Americans Bruce Cree, Farren B. Briggs, Stacey
J. Callier, Lisa F. Barcellos, Patricia R. Ramsey, Stephen Hauser,
Jorge Oksenberg

Much of this presentation went a bit over my head, so I don't know
if I caught the full gist of it. What I gathered was that in this
special population of African Americans with MS, they found that
HLA-DRB5 was not required for MS susceptibility and when present
reduced the severity conferred by DRB1*15. A SNP in the AGER gene
found to be associated with MS, but is unlikely to be causative.

2:30 P.M. S42.005 ABC-Transporter Gene Polymorphisms:
Potential Predictors of Therapeutic Efficacy of Mitoxantrone in
Multiple Sclerosis Steffi Cotte, Niels Kruse, Nicolas Von
Ahsen, Uwe Zettl, Neus Tellez, Xavier Montalban, Ralf Gold, Andrew
Chan

This study looked to see if they could find genetic markers
associated with response to mitoxantrone in MS. They seemed to find
two genes that are associated with increased response.

2:45 P.M. S42.006 Cortical Pathology and Meningeal
Inflammation in Early MS Shanu F. Roemer, Natalia Moll,
Richard M. Ransohoff, Brendan Kelley, Joseph E. Parisi, Claudia
Lucchinetti

Looking at samples from humans, I believe from biopsy material (and
maybe some post-mortem), this study found that cortical demyelination
is present early in MS and that the cortex can be the initial target
of MS. They found that early cortical demyelination was inflammatory
(immune cells present), and that meningeal demyelination is mostly
diffuse, but can be focal and is also inflammatory.

3:00 P.M. S42.007 The Multiple Sclerosis Susceptibility
Allele in the IL2RA Locus Correlates with Higher Soluble IL2-RA
Expression Lisa Maier, Christopher Severson, International MS
Genetic Consortium, David Hafler, Philip De Jager

The recent finding of association of IL2RA SNPs with MS has lead to
further investigations like this one. It turns out that Type 1
Diabetes (T1D) also has associations with SNPs in this gene area.
Looking at the overlap, they found that one SNP in T1D was not related
to MS at all, one was associated with MS but was protective in T1D,
and they had one shared risk allele.

They also saw that those who had the susceptibility allele had
higher levels of soluble IL2RA (the protein that the gene codes for)
when compared to controls. This could provide a clue for future
treatments.

3:15 P.M. S42.008 An Extremes of Outcome Strategy Provides
Evidence for Multiple Sclerosis Severity Being Determined by Alleles
at the HLA-DRB1 Locus Gabriele C. De Luca, Sreeram V.
Ramagopalan, Blanca M. Herrera, David A. Dyment, Matthew R. Lincoln,
Alexandre Montpetit, Maura Pugliatti, Neil Risch, Dessa Sadovnick,
Margaret Esiri, Stefano Sotgiu, Thomas J. Hudson, George Ebers

This study looked at the genetics of people with extremes of MS
severity (malignant vs benign): those with an EDSS >= 6 within 5
years of onset, and those with EDSS < 3 after 20 years. The hope
was that there would be a stronger signal from these populations than
from the whole spectrum of MS outcomes. While there was a little
signal, they didn't find an association with any SNPs they looked at.
They did find some evidence that DRB1*01 is protective for risk of
progression.

S50 MULTIPLE SCLEROSIS: IMMUNOLOGY III (Hollie)

1:30 P.M. S50.001 Abnormal T Cell Reactivities in Childhood
Inflammatory Demyelinating Disease and CNS Injury Brenda
Banwell, Roy Cheung, Julia Kennedy, Lauren Krupp, Dorothy Becker,
Hans-Michael Dosch, Wadsworth Pediatric MS Study Group, Amit Bar-Or

Dr. Banwell presented the results of a study that tested T cell
proliferation in response to various antigens. Included in this
study were pediatric subjects with MS, CIS (a single MS-like
symptom), Type 1 diabetes, other neurological conditions, and healthy
controls. They found that MS, CIS, T1D, and OND subjects all
responded to MBP antigens but healthy controls generally did not.
Neither T1D subjects nor controls responded to MOG antigens. MS/CIS
and T1D subjects responded to milk epitopes but healthy controls
didn't. Interestingly, the MS/CIS subjects responded to different
milk antigens than the T1D group did. The team concluded that the
presence of myelin autoreactive T cells is a normal response to
injury, but still to be determined is what type of T cells are
proliferating (are they pro- or anti-inflammatory T cells, for
instance?).

1:45 P.M. S50.002 Blockade of LRG-47 Promotes Apoptosis and
Suppresses Induction of Experimental Autoimmune Encephalitis
Hong Wei Xu, Zhiying Wu, Lan Guo, Doris Chen, John Xi Chen, Shi Du Yan

A protein called LRG-47 that has antimicrobial functions is more
strongly expressed in MS subjects vs. controls (8-10x more expression)
as well as in EAE mice vs. control mice (30x). This suggests that
LRG-47 may be involved in MS pathogenesis. This team induced EAE in
LRG-47 knockout mice, and found that they developed almost no EAE
clinical symptoms, there was less infiltration of immune cells into
the brain, and more of these cells were apoptotic. These knockouts
also had a lower T-cell proliferatory response in response to MBP than
control mice. The researchers have developed a small interfering RNA
(siRNA) to LRG-47 which also attenuated EAE in normal mice. So it
seems that this protein is worth further study.

2:00 P.M. S50.003 Evaluation of a Leukocyte Population
Modulator (LPM), OPL-CCL2-LPM, in Experimental Autoimmune
Encephalomyelitis (EAE) Smriti Agrawal, Trina Johnson, Claudia
Silva, John McDonald, Laura McIntosh, Philip Coggins, Wee V. Yong

Here's another potential MS therapy in the works: OPL-CCL2-LPM
selectively targets and kills immune cells that express CCR2.
(“Leukocyte Population Modulator” must be a euphemism for
“Cell Assassin”!) Preliminary studies in EAE shows that
it diminishes or delays the onset of symptoms, reduces cellular
infiltration, and reduces demyelination in the spinal cord. Next
steps for research with this molecule include determining the correct
dosage and understanding its mechanism of action.

2:15 P.M. S50.004 Studies of Oligonucleotide- Based
Antagonists of TLR9 in a Mouse Model of Experimental Autoimmune
Encephalomyelitis Fu-Gang Zhu, Ekambar R. Kandimalla, Dong Yu,
Agrawal Agrawal

There is evidence that toll-like receptors (TLRs), a class of
molecules involved in the immune system, may play a role in MS and
similar diseases. This study showed that a molecule developed to
block TLR9 appears to reduce EAE symptoms, inflammation, and
demyelination.

2:30 P.M. S50.005 IL-7 Receptor Alpha Chain Discriminates
between a Normal Regulatory and a Hyperproliferative Proinflammatory T
Cell Subset in Patients with Relapsing- Remitting Multiple
Sclerosis David A. Laplaud, Laure Michel, Laureline Berthelot,
Sandrine Wiertlewski, Pettré Ségolène, Fabienne
Lefrère, Sophie Brouard, Jean-Paul Soulillou

CD4+/CD25high T cells are normally regulatory cells that work to
inhibit immune responses. However, cells of this type from MS
subjects have lower inhibitory capacity than those from controls. It
turns out that a subset of these cells also express CD127 and are
hyperproliferative and pro-inflammatory. When these cells are
removed, CD4+/CD25high cells from MS subjects have similar regulatory
properties as those from controls.

2:45 P.M. S50.006 Is Multiple Sclerosis Disease Activity, as
Detected by Gadolinium-Enhanced MRI, Associated with Virological and
Immunological Evidence of EBV Reactivation in the Peripheral
Blood? Rachel Farrell, Dinu Antony, Duncan Clark, Fisniku
Leonora, Josephine Swanton, Alan Thompson, David Miller, Gavin
Giovannoni

This study investigated whether periods of Epstein-Barr virus
reactivation were associated with MS activity or disease course.
Blood was drawn from 25 RRMS subjects, 25 PPMS subjects, and 50 CIS
subjects at different timepoints and analyzed for the presence of EBV
DNA and antibodies to EBV. PPMS subjects had higher levels of
antibodies to the EBV antigen VCA, while RRMS subjects had higher
levels of antibodies to EBNA. Levels of anti-EBNA-1 IgG were higher
in subjects with Gd+ lesions but there was no significant correlation
between Gd+ lesions and presence of viral DNA or anti-VCA IgM..

3:00 P.M. S50.007 Molecular Response to Interferon Beta in
Multiple Sclerosis: A Longitudinal Study Richard A. Rudick,
Sandhya Rani, Yaomin Xu, Jennifer Shrock, Jar-Chi Lee, Richard
M. Ransohoff

In this study, the expression of 197 interferon-responsive genes
was measured in 35 MS subjects at the beginning of IFN-b therapy and
six months later. A set of genes was found that seemed to be
consistently upregulated by IFN-b in almost all of the subjects. No
general relationship between clinical response and magnitude of the
gene expression response, or stability of the response over time,
could be found. The presence of viral infections and neutralizing
antibodies did affect gene expression, however. The researchers are
now looking for individual genes whose expression might be correlated
with clinical response to IFN-b.

3:15 P.M. S50.008 Cognition and Cerebellar Dysfunction in
Multiple Sclerosis Are Associated with Decreased Bri2
Expression Pamela I. Good, Niamh B. OHara, Nara Chhua,
Violaine K. Harris, Saud Sadiq

Proteomic analysis of CSF from MS subjects revealed that a peptide
called Bri-CT (part of the Bri2 protein) was less abundant in the CSF
of SPMS and PPMS subjects compared with controls. Because genetic
variants of the Bri2 gene are associated with familial dementia, it
occurred to these researchers that Bri2 might be associated with
reduced cognitive or cerebellar function in people with MS. They did
find that Bri-CT levels in the CSF were decreased in MS subjects with
decreased cerebellar and/or cognitive function. Furthermore, BRI2
expression in the cerebellum (but not the hippocampus) was lower in 10
MS brains than in 10 control brains.

S52 MULTIPLE SCLEROSIS: OUTCOMES (Art)

3:45 P.M. S52.001 Asymptomatic Demyelinating Disease The
Radiologically Isolated Syndrome (RIS): Longitudinal Clinical Data
Extending 12 Years Darin T. Okuda, Azedeh Beheshtian,
Emmanuelle Waubant, Ellen Mowry, Ari Green, Bruce A. C. Cree, Douglas
S. Goodin, Stephen L. Hauser, Daniel Pelletier

In an attempt to create a new category for the spectrum that is
demyelinating disease, is the new term RIS. RIS is seen in clinical
practice when someone is given an MRI for another reason (e.g
migraines, research controls, sibling with MS) and evidence of WM
abnormalities are found that are consistent with MS.

After following a number of these patients for years, they found
that many of the RIS patients convert to CIS after a mean of 6.7
years. Of course, CIS can convert to MS. They will be longitudinally
following this cohort in a detailed study.

4:00 P.M. S52.002 CNS Aquaporin-4 Autoimmunity in
Childhood Andrew McKeon, Vanda Lennon, Timothy Lotze, Silvia
Tenembaum, Jayne Ness, Mary Rensel, Nancy Kuntz, James P. Fryer,
Henry Homburger, Jill Hunter, Brian Weinshenker, Karl Krecke, Claudia
Lucchinetti, Sean Pittock

This was a description of a cohort of pediatric subjects who tested
positive for the NMO IgG antibody. They presented clinical and
radiological findings.

4:15 P.M. S52.003 Retinal Nerve Fiber Layer (RNFL) Thickness
and Total Macular Volume (TMV) in Multiple Sclerosis, Neuromyelitis
Optica, and Clinically Isolated Syndromes John Ratchford,
Girish Hiremath, Eliza Gordon-Lipkin, Mathew Pulicken, Gary Cutter,
Douglas Kerr, Laura Balcer, Peter Calabresi

A lot of researchers are looking into using OCT measures of retinal
nerve fiber layer thickness as a surrogate for brain atrophy. It is
cheap, fast, and easy to do and could replace MRI for certain aspects
of monitoring MS progression.

This study looked at people with MS, CIS/TM, NMO, and controls. In
the MS group they found that all subjects had abnormal RNFL thickness
compared to controls. There was more thinning the longer the disease
duration - approximately a 1% thinning per year of disease.

In the NMO group they found that there was 4X the thinning seen in
MS, but only in eyes that experienced optic neuritis (ON). The non-ON
eyes were normal. The CIS/TM group was similar to controls.

One comment during the question period brought up the idea that the
regularly rate of thinning in MS might be useful to project backwards
in time to get an idea of when someone's MS actually started.

4:30 P.M. S52.004 Genomic Effects of Interferon- Treatment
after the First Dose and on Chronic Dosing: Relationships to 5-Year
Clinical Outcomes in Multiple Sclerosis Patients Bianca
Weinstock-Guttman, Kavitha Bhasi, Darlene Badgett, Miranda Minhas,
Joan Feichter, Kara Patrick, Fredrick Munschauer, Rohit Bakshi, Murali
Ramanathan

This study looked at 22 subjects for 5 years who were on IFN
treatment for their MS. Good responders were considered those with no
relapses and no EDSS increase in the first 2 years of treatment. They
looked at gene expression profiles after the first dose and after
chronic dosing. They found some differences in biological reaction to
the drugs that may allow prediction of who will be a good responder.
Of course, larger studies are needed.

4:45 P.M. S52.005 Evidence of Axonal Loss in Clinically
Isolated Syndromes by Optical Coherence Tomography? Olivier
Outteryck, Hélèhe Zéphir, Sabine Defoort,
Philippe Debruyne, Ikram Bouacha, Arnaud Lacour, Didier Ferriby,
Pierre Labalette, Jérome De Séze, Patrick Vermersch

This study looked at 56 CIS and 32 controls using MRI, visual
evoked potential, and OCT. OCT did not show a significant difference
from controls.

S60 MULTIPLE SCLEROSIS: IMAGING II (Hollie)

3:45 P.M. S60.001 Multiple Sclerosis Lesion Localization and
Characterization by 7 Tesla Magnetic Resonance Imaging
Francesca Bagnato, Vasiliki Ikonomidou, Peter van Gelderen, Joan
Ohayon, Susan Fulton, Mary Ehrmantraut, Henry McFarland, Jeff H. Duyn

Dr. Bagnato showed some slides of MS brains taken using a 7T MRI
system. She said that 7T shows lesions and individual features of
lesions that are not visible at lower strengths, such as ring
enhancement and heterogeneity of structure within single lesions. The
7T MRI process seems to be safe and well-tolerated. (Personal note: I
participated in a 7T study as a control and while it did make me dizzy
for a little while afterwards, the images are really amazing.)

4:00 P.M. S60.002 Optic Disc Measurements by OCT in Multiple
Sclerosis: Relation to Retinal Nerve Fiber Layer Thickness and Visual
Function Esther Bisker, Amy Conger, Amber Salter, Teresa
Frohman, Steven Galetta, Clyde Markowitz, Gary Cutter, Gui-Shuang
Ying, Maureen Maguire, Peter Calabresi, Elliot Frohman, Laura Balcer

Optical imaging techniques have gained a lot of attention recently
for their potential to assess MS axonal damage in a non-invasive,
cost-effective way. This study used one such technique, OCT, to
determine whether optic disk measurements distinguish MS from control
subjects, and whether they correlate with visual function and/or
retinal nerve fiber layer thickness (RNFL). Three optic disk
measurements distinguished the MS subjects from the controls: rim
area, average nerve width at the disk rim, and horizontal integrated
rim width. These measurements were also associated with visual
dysfunction and RNFL thinning; however, RNFL measurement was a better
differentiator between MS and controls. Other features such as
cup/disk area ratio were able to distinguish between MS eyes with or
without a history of optic neuritis.

4:15 P.M. S60.003 Gray Matter Damage on Brain MRI Scans Is
Associated with Clinical Progression in Multiple Sclerosis
Mohit Neema, Ashish Arora, Brian Healy, Zachary D. Guss, Steven Brass,
Yang Duan, Guy Buckle, Bonnie Glanz, Lynn Stazzone, Samia Khoury,
Howard Weiner, Charles Guttmann, Rohit Bakshi

Hypointense regions on T2 MRI images are likely to represent
increased iron deposition. This study investigated the relationship
between T2 hypointensity and progression. 97 MS subjects were
followed for 4.5 years, and 32% of them experienced some progression
during this time. Out of several measures analyzed, only T2 intensity
change in gray matter regions (caudate, putamen and thalamus)
correlated with progression. Brain parenchymal fraction (overall
brain atrophy) and T2 lesion volume did not correlate with
progression. This suggests a role for iron deposition in the
pathogenesis of MS, either as a marker or as a mediator. Perhaps iron
is a potential source of free radical oxidation? New techniques are
being developed to specifically measure iron deposition in the
body.

4:30 P.M. S60.004 Structural and Functional Hippocampal
Changes in Multiple Sclerosis Nancy L. Sicotte, Kyle C. Kern,
Yonggang Shi, Amrapali Arshanapalli, Michael Montag, Barbara S.
Giesser, Arthur Toga, Susan Y. Bookheimer

Changes in the hippocampus in MS have important implications for
memory function. Dr. Sicotte presented 3D images made using a surface
mapping technique which identified areas of atrophy within the
hippocampus, mainly in SPMS subjects. She also had some MS subjects
performed neuropsych exercises (such as word learning) while in a
functional MRI set-up; good performance was associated only with very
localized hippocampal activation while poor performance was associated
with more widespread and bilateral activation.

4:45 P.M. S60.005 Prospective MRI Study of Brain Atrophy and
Its Relationship to Disability in a Murine Model of MS Istvan
Pirko, Jeremiah McDole, Yi Chen, Scott Dunn, Diana M. Lindquist, Aaron
Johnson

This study of the Theiler's mouse model of MS showed that brain
atrophy preceded disability, and is probably driven by axonal and
neuronal loss.

At the end of the day on Thursday, Kristin packed up the booth and
we all went to the airport. Our flight was on time and we met a few
AAN attendees we knew who were heading back to Boston while we waited.
Luckily all our luggage made it back safely and so did we!