Art's & Hollie's Notes from 2006 AAN in San Diego

Art's and Hollie's Notes From the 2006 AAN Meeting in San Diego

Thu 03/30:

Art got up at 4:30am to go to the airport to fly to San Diego. Flight was on time and uneventful. Since he used to live in San Diego for a few years (20 years ago), Art went out a little early with his wife to check out the old stomping grounds.

We got in, went to the hotel, drove around a bit, and had dinner with some donors.

Fri 03/31:

Friday was a vacation day.

Sat 04/01:

More vacation and visiting with old friends.

Sun 04/02:

Debbie left, Art took advantage of the high-speed internet to catch up on some work. Changed hotels and cars to get ready for the coming week.

Mon 04/03:

Julie and Art went over to the convention center to register and set up our booth. We then took a little drive around the area and came back to the hotel to get some work done.

Later that evening we had to return to staff the booth for the opening of the show. We saw Ben and Chitra from Johns Hopkins, Judy from Teva, and met a number of others who were interested in what we were doing.

After fighting through the crowds pouring out of the Padres opening day game (across the street from the convention center), we made our way back to our hotel to catch up on email.

Meanwhile, Hollie flew in and arrived at the hotel at 9:00 pm only to find out the reservation had gotten messed up and she had to stay at a different hotel for that night since the original one was full. Such is the glamorous life of the business traveler.

Tue 04/04:

Art got up early to deal with a variety of business issues back at the office and then went to a lunch meeting of MIT Alums to speak about the Accelerated Cure Project. Hollie went to catch the end of the plenary session and heard from, among other speakers, David Brailer, the federal government's health IT czar.

During the remainder of the week, Julie Morgenlender and volunteer Randy Smith staffed our booth in the exhibit hall, answering questions about our organization and handing out materials.

In the afternoon were the scientific sessions which Art and Hollie attended.

Clinical Trials I (Art)

MBP encoding plasmid with and without atorvastatin
Tim Vollmer

This described a Phase 1 trial of a an MBP encoding plasmid (circular piece of DNA) with and without atorvastatin. It's a drug called BHT-3009 made by Bay Hill Therapeutics. They believe it may be able to induce tolerance and immune deactivation toward myelin. The trial was small and done on people with RRMS and SPMS. There were some side effects like depression, but no safety concerns. They are starting a Phase 2 trial.

Antigen specific immunomodulation in MS treated with BHT-3009
Amit Bar-Or

This phase 1 trial was done on people with RRMS and SPMS using a drug called BHT-3009 from Bay Hill Therapeutics. The theoretical mechanism of action for this drug is to vaccinate people with a plasmid (circular piece of DNA) containing the gene for MBP (thought to be an antigen in MS) so that it is taken up by antigen presenting cells. They will then express MBP internally and present them on their surface without co-stimulatory signals which will then induce tolerance for the protein. This should stop T-cells from attacking myelin.

The study was done with 12 people on placebo and 28 on active drug. Adverse events included depression and some others, but no real safety concerns emerged. They are starting a phase 2 study.

Effects of natalizumab (Tysabri) on disability progression in MS
Ted Phillips

This presentation largely went over data that had been made public previously, but is worth mentioning again here. In the Tysabri monotherapy trial 627 subjects received active drug, 315 placebo. 29% of placebo and 17% of Tysabri recipients had a sustained increase in EDSS. There were a lower percentage of people on Tysabri reaching EDSS of 5 and 6 than placebo. MSFC showed a slight improvement on Tysabri and worsening on placebo, more from 3 hole peg test and PASAT, while timed walk showed worsening (but less than placebo).

Safety profile of mitoxantrone in 802 MS patients in France over a 5 to 12 year period
Emmanuelle Le Page

Basically, they have been using mitoxantrone (Novantrone) on a lot of people for a long time and have not had too many serious adverse events. They did see cardiac abnormalities in 5% of the people, had one case of AML (a type of blood cancer) that resulted in a death, and one case of AML that did not. Transient and persistent amenorrhea (loss of period) were relatively common, with an increasing risk after the age of 35.

Imaging I (Hollie)

Composite MRI score as a biomarker in clinical trials in MS
Anthony Traboulsee

This group explored the question of whether MRI data can be used to predict or serve as a surrogate for time to confirmed disability in clinical trials. Individual measurements have not yet been found adequate for these purposes, but perhaps a combination of measurements would be more useful. Using disability and MRI data from a recent trial, the team found that combining the number of active T2 lesions (high or low) and T2 lesion volume change (high or low) at the 12-month checkpoint could predict disability change at the 24-month checkpoint. A plan is now in place to validate this scheme using 8-year checkpoint data and data from other studies.

Evaluation of the cervical spinal cord in MS with high resolution magnetization transfer MRI at 3T
Seth Smith

Imaging of the spinal cord has not been conducted as extensively in MS as imaging of the brain, but some scientists are doing their best to catch up. This presentation discussed a higher resolution technique that apparently can detect more lesions and allows individual fibers in the spinal cord to be tracked. More work is needed to make sure that the additional lesions detected with this method are real and not just artifacts of the technique.

Normal appearing white matter and gray matter glutamate in MS from multi-voxel spectroscopy maps at 3T
Radhika Srinivasan

This presentation described a new magnetic resonance spectroscopy method that can detect glutamate in the brain (with previous methods, the glutamate signal could not be separated from the signals of other molecules). Glutamate is a neurotransmitter that in excess quantities can be harmful to nerve tissue - it may play a role in MS. An initial study had found that glutamate concentrations were higher in normal appearing white matter (NAWM) and acute lesions of MS subjects than in chronic MS lesions or white matter from control subjects. The new data confirmed the increase in NAWM but showed no significant difference in glutamate concentrations between MS and control gray matter, and no correlation between NAWM glutamate and brain volume. The speaker hypothesized that the reason why glutamate is increased in MS normal appearing white but not gray matter is because there are more inflammatory cells in NAWM (but an audience member questioned whether there could be enough such cells in NAWM to produce this large of a difference).

Multi-slice brain myelin water fractions at 3T in MS
Daniel Pelletier

A technique to assess water molecules in myelin layers (myelin water fraction, or MWF) has been tested in 89 MS subjects and 28 controls. MWF was significantly lower in MS NAWM than control white matter, even in people with disease duration of five years or less. MWF was even lower in acute and chronic lesions. Modest correlations were found between MWF and lesion volumes, but there was little correlation between MWF and EDSS. The team now plans to use this technique in longitudinal studies and combine the results with other types of imaging data.

Pattern of hemodynamic impairment in MS: Dynamic susceptibility contrast perfusion imaging at 3T
Matilde Inglese

Perfusion MRI was used to study blood flow and blood volume in subjects with PPMS and RRMS and controls. Both cerebral blood flow and volume were highest in controls and lowest in PPMS subjects. (Could microvascular abnormalities be involved in the degeneration seen in PPMS?) Some correlations were found between blood flow and volume and EDSS, but not with lesion volume or disease duration. An audience member asked the correlation with EDSS could work in reverse - could having higher disability lead to lower cardiovascular fitness which could produce microvascular abnormalities? (The speaker thought not on the basis of the clinical data from the subjects, but couldn't rule it out.)

Corpus callosum index: A practical measure for long-term follow-up in MS
Fernando Figueira

This speaker proposed using the corpus callosum index (a measurement of the thickness of the corpus callosum) in evaluating neurological damage in MS patients over time. Data shows that this measurement correlates well with brain volume, as well as with cognitive disability in RRMS and SPMS subjects. This measurement does not require sophisticated image processing to determine, and thus may be practical in settings lacking the required software.

Neurogenetics (Hollie)

Dissection of the admixture MS susceptibility locus on chromosome 1 to a 4 MB interval in an African-American population
Philip De Jager

The prevalence of MS in the African-American population is 1 in 2,000 whereas in Africans it is 1 in 100,000. It is thought that the 20% of the African-American genome that comes from European ancestry is responsible for this increase in risk. An ongoing research project is looking for the presence of European genetic variants in African-American MS and control subjects to see if any are over-represented in the MS group and thus may be MS risk factors. The team has found a region on chromosome 1 where MS cases tend to have more European variants, but has not yet narrowed the region down to pinpoint the responsible location. The team has also determined that the degree of European ancestry in an African-American with MS appears to have little effect on age of onset.

Clinical Trials II (Art and Hollie)

The Dystal Prize

The AAN and MS Society give a prize out each year to a leader in MS research. This year the recipient was William Sibley. He gave a talk on the possibility of MS as a post-infectious disease and viruses as a trigger of MS. He mentioned some interesting findings Art hadn't heard before such as that people with MS have fewer clinically evident infections than controls and that people with more infections seem to progress more slowly (opposite to what you would expect).

Tracking relapses by month, there seem to be peaks in April and August (Art's relapses fall into those months). Also, optic neuritis has a lull in Jan-Mar and peaks in Apr-Jun, which correlates with rhinovirus infections. Sibley mentioned a small study that correlated rhinovirus infections with exacerbations, and said that the study was now being repeated in a larger sample based in Utah and Arizona.

Oral FTY720 (fingolimod) in RRMS phase 2 extension study
Paul O'Connor

Previously we reported on the FTY720 results; this talk released the results of a 12 month extension study performed with RRMS and SPMS subjects. Mean Gd+ lesions were reduced 40-60% (depending on dose) and mean relapse rates were reduced 55%. The drug appeared to significantly reduce the number of lymphocytes circulating in the bloodstream to 25-30% of baseline amounts. 70% of subjects were free of Gd+ lesions at month 12. The larger 5mg dose had more serious adverse events (although there did not seem to be a pattern among the SAEs), so future trials will be going with 1.25mg as there did not seem to be a significant difference in efficacy between the doses. A phase 3 trial has been initiated in Europe.

Intravenous synthetic peptide MBP8298 delayed progression in HLA class 2 defined subjects with progressive MS
Ingrid Catz

This 24 month trial with 5-12 year followup gave infusions every 6 months of a drug that is believed to create antigen-specific tolerance to MBP. The drug is a sequence of human MBP, containing amino acids 82-98, and appears to inhibit the formation of MBP autoantibodies in the central nervous system. In 20 subjects with HLA-DR2 and/or DR4 (a genetic marker), 0 of 10 subjects receiving active drug progressed vs. 4 of 10 subjects on placebo. The investigators saw a delay in progression of 60 months (78 months for active drug, 18 months for placebo). There were no serious adverse events, and a larger trial is in progress.

Induction of CD4+CD25+ (regulatory) T-cells with blockade of CD154 in RRMS
Lloyd Kasper

This phase 1 trial of Idec-131 on 12 subjects over 18 weeks with 5 years of followup resulted in stable EDSS and only modest progression of MRI results. This drug is a humanized antibody to CD154, a protein that is expressed on T cells and interacts with CD40 on antigen-presenting cells during immune system activation. The speaker noted that his team no longer has access to this drug for follow-up trials and it is unclear whether Idec wants to pursue further trials.

After the talks we went and checked out some of the posters researchers were presenting and ran into a number of people we wanted to talk to.

We then took one of our donors out to dinner after visiting her place of work - the San Diego Humane Society - where we got to see all the cute dogs, cats, bunnies, and guinea pigs.

Wed 04/05:

Art and Hollie headed over to the convention center to check out the morning poster session. Art took the time to log in from the center to do MSNews.

At lunch Art met with Chitra Krishnan from Johns Hopkins to discuss participation in the conference they will be running this summer.

In the afternoon there were more presentations. Art attended the Animal models track of MS sessions which were very much over his head and involving material that was so distantly related to humans in most cases that human MS was not even mentioned. He left early to finish canvassing the exhibit hall. A noteworthy point was Howard Weiner's study in EAE of an oral anti-CD3 monoclonal antibody that will be going into phase 1 with humans soon.

Imaging II (Hollie)

A composite MRI score (Z4) predicts disability over the next 4.5 years in a prospectively followed cohort of subjects on glatiramer acetate
Jerry Wolinsky

This presentation concerned another composite MRI measurement (called Z4 and composed of characteristics such as lesion volumes) that was developed as a possible predictor/surrogate of future accumulation of clinical disability. Comparison of MRI and clinical data gathered during a Copaxone study showed that subjects who started out in the worst Z4 quartile wound up significantly worse after 4.5 years in terms of EDSS than the other subjects. So perhaps this measurement has some utility for predicting more severe progression. It was also noted that subjects who had more Gd+ lesions tended to have more relapses but this had no correlation with disability progression.

MRI intensities correlate with immunopathologic patterns in MS
Bradley Erickson

Previous pathology studies have reported that MS lesions tend to fall into one of four patterns based on the type of damage and the cells/factors found at the site. This raises the question of whether the lesion pattern in an individual can be determined by MRI rather than invasive biopsy techniques. This research team performed clinical and MRI assessments of 72 MS subjects who had undergone lesion biopsy and pattern classification (types I, II and III were represented). Comparing the MRI results with the pattern types, they found differences in lesion image intensity (but not lesion volume) between type III and the other two types (I and II). The data also suggested differences in the NAWM between patterns -- greater destruction and less repair was suggested in the type III images, which is consistent with the tissue studies. As with the pathology studies, repeat MRIs performed some time after the initial ones indicated that the patterns tend to persist in individual subjects rather than changing over time.

Retinal periphlebitis and optic nerve fiber layer atrophy is associated with disease activity in MS
Pablo Villoslada

A two-year study of a technique called OCT (optical coherence tomography) was carried out to measure retinal nerve fiber layer (RFNL) thickness in people with MS and healthy controls. RFNL thickness was decreased in MS subjects vs. controls, and was also decreased in MS subjects that had experienced optic neuritis vs. those that had not. Lower RFNL values was correlated with EDSS as well as relapses during the next two years, indicating that this measurement may also be a good surrogate of clinical activity and progression.

MRI brain lesions characteristic of neuromyelitis optica (NMO) colocalize with sites of high aquaporin protein characteristics
Sean Pittock

A recent well-publicized finding in NMO concerns the detection of an autoantibody to the protein aquaporin 4 that appears to be a marker for the disease. Aquaporin 4 plays a role in the transfer of water in and out of cells, and is found in astrocytes in the spinal cord, but is also highly expressed in certain areas of the brain. The classic definition of NMO includes no brain lesions -- however, this review of MRIs from people who had received an NMO diagnosis did find brain MRI abnormalities in some. Interestingly, these abnormalities tended to be found in sites rich in aquaporin 4 such as the hypothalamus. The speaker noted that the NMO diagnostic criteria are currently being updated to include the aquaporin 4 antibody and revised MRI guidance.

Brain compensation for cognitive processes in MS: A fMRI study
James Bowen

A functional MRI study of cognitive ability in RRMS (15 MS subjects with a mean EDSS of 4.5, 10 controls) found no differences in brain activation between the groups when the subjects performed finger tapping exercises. However, significantly greater brain activation was seen in the MS group when performing a logical reasoning test. The MS group also reported a higher level of exertion on this test compared with controls. Although the performance on the test was similar between the two groups, the fMRI results suggest that people with MS who report cognitive impairment but perform normally on cognitive tests may be experiencing impairment in terms of greater expenditure of effort.

The radiographic spectrum of biopsy proven inflammatory demyelinating disease
Claudia Lucchinetti

This presentation was a retrospective review of MRI scans from people who had biopsies performed to confirm the presence of inflammatory demyelinating disease (most were eventually diagnosed with MS). Most of the biopsied lesions were from frontal/parietal regions of the brain and the majority were described as tumefactive (i.e., swollen, greater than 2 cm in diameter), which is probably the feature that prompted the biopsy. However, the presence of large lesions did not necessarily imply more severe progression.

Clinical Trials/Immunology (Art and Hollie)

Immune surveillance in MS treated with Tysabri
Olaf Stuve

This study looked at immune system parameters in 23 people with MS who had been on Tysabri and compared them to people with other neurological diseases, MS subjects without Tysabri, and people with HIV. The investigators found that Tysabri appeared to decrease the level of CD4+ and CD8+ T cells and CD19+ and CD138+ B cells moving from the peripheral blood to the CSF; also, the CD4/CD8 ratio in Tysabri subjects was very low in CSF while normal in the peripheral blood. This suggests that Tysabri works as the models suggested, by decreasing the immune surveillance activity in the central nervous system.

Immunization with trivalent T-cell receptor peptide vaccine increases FoxP3 expression in CD4+CD25+ cells in MS
Dennis Bourdette

This study involved TCR (T cell receptor) peptide vaccination using NeuroVax. This vaccine was developed to induce the production of T regulatory cells (CD4+CD25+ T cells) that maintain tolerance in autoreactive T cells. Development of the vaccine has been slow due to low immunogenicity, but a more effective formula was recently developed. T regulatory cells are decreased in the blood of people with MS and are associated with expression of the FoxP3 gene. In this trial, 13 of 17 people on NeuroVax showed an increase in FoxP3 expression (to levels equivalent to or higher than those seen in healthy controls) which may indicate how this vaccine might work. A phase 2 trial with 300 subjects is scheduled for late 2006.

FTY720 in RRMS: Mechanistic exposure-lymphocyte model and relationship to efficacy
L. Kappos

As mentioned in a previous presentation, FTY720 decreases the numbers of circulating lymphocytes in the bloodstream; it does so by trapping these cells in lymph nodes. This presentation reviewed trial results that supported the ability of this drug to reduce T cell counts, but did not show a correlation between degree of reduction and clinical efficacy. So perhaps another mode of action is taking place with this drug. In response to a question, the speaker noted that long-term trapping of T cells in lymph nodes was not expected to lead to medical problems - this opinion was based on experiences with administering this drug to transplant patients.

Tysabri reduces loss of visual function in RRMS
Laura Balcer

A low contrast (gray on white) letter acuity test was developed to assess visual function and was found to reflect axonal loss as verified by optical coherence tomography (OCT). It seems to be a more sensitive indicator of optic change than high contrast tests and has been shown to add specificity to the MS functional composite (MSFC). Can it also be used as an outcome measure in clinical trials? A research team found that use of this test was able to effectively distinguish between the treatment arms in the AFFIRM and SENTINEL Tysabri trials. The team will now determine whether this test can contribute to the use of MSFC in MS treatment trials.

Circulating interferon inhibitors may adversely affect outcomes in MS patients who do not have neutralizing antibodies
Bianca Weinstock-Guttman

This presentation addressed the question of why some people don't do well on interferon-beta drugs despite not having developed any neutralizing antibodies. Previous studies of cancer patients had suggested the presence in some patients of something called "interferon inhibitory activity" (IIA). Healthy people don't have IIA but people with certain medical conditions may have it. In this study, 38 people with MS who were on IFN-b donated serum which was exposed to IFN-beta and evaluated for antiviral activity. Interferon inhibition was higher in those subjects characterized as partial IFN-b responders than in those who were good responders. Testing for IIA may turn out to provide a good biomarker for IFN response and disease activity. The team is now trying to determine what IIA is exactly (what molecules are involved, etc.) since this is not yet known.

Thu 04/06:

Art and Hollie went to the "W" Hotel (which seems to think it is the coolest hotel in the world based on its decor, employee dress, and music) to meet up with Tim Vollmer from Barrow in AZ. There was a bit of a mix up and Hollie ended up going to meet him at the convention center. Art had to stay and meet with a donor he had previously arranged to meet there.

After, Art went to the convention center, got lunch, took some phone calls for East Coast business things, and went to check out a computer based neuro-psych system that might possibly be useful for our repository in the future.

Immunology (Art and Hollie)

T-cell proliferation against myelin, pancreatic, and dietary antigens in children: autoimmunity is detectable early in CNS demyelination and type I diabetes
Brenda Banwell

This presentation explored the T cell immune response to self-antigens and dietary antigens in children with MS, clinically isolated syndromes, and diabetes. As expected, the MS and CIS groups had an elevated immune response to myelin and glial antigens, and the diabetes group showed a response to those antigens as well as pancreatic antigens. The MS/CIS group reacted to a particular milk antigen but not egg antigens; the diabetes group had a high response to a different milk antigen. This shows that there are some differences in target antigens between autoimmune diseases, although there is also overlap. Interestingly, the subjects who did not appear to react to the milk antigens tended not to react to self-antigens either.

Elevated T-cell production of IL-17 in transverse myelitis and MS leads to induction of astrocyte IL-6
Jerome Graber

The gist of this presentation was that T cells in subjects with TM and early MS produce IL-17 which induces macrophages to release IL-6 which induces astrocytes to release even more IL-6 which may contribute to neurological damage.

Detection of serum immunoglobulin (Ig)E reactive against myelin protein-derived peptides in MS patients
Daniel Mikol

Mast cells play a key role in allergic reactions and have also been found in the brains of people with MS. Activation of mast cells require binding by a form of antibody called IgE which has not been extensively studied in MS. This study found increased levels of IgE against myelin peptides in the serum of MS subjects compared with controls. Furthermore, there was a larger percentage of MS subjects than controls who were positive for anti-myelin IgE but negative for anti-myelin IgG and IgA which could block the binding of IgE to mast cells. This suggests that MS subjects are more likely than controls to have mast cells activated against myelin antigens. The speaker recommended that future antibody studies in MS consider a wider range of antibody forms including IgE.

Quantitative titers of anti-MOG antibodies correlate to disease severity in RRMS
Til Menge

MOG is a protein on the outside of myelin and is hypothesized to be one of the targets in MS for autoimmunity. There is a high titer (level) of anti-MOG antibodies in 15% of RRMS subjects which correlates with disease severity. The author hypothesized that this might identify a subset of people with RRMS that is driven by B cells instead of T cells.

Characterization of T-Cells derived from acute and chronic MS lesions
Silva Markovic-Plese

A research group had the opportunity to characterize the T cells in several acute and chronic lesions in post-mortem brain tissue from a young woman with MS who died suddenly. This was the first such study that has been performed using post-mortem tissue. Characteristics assessed included T cell receptor gene repertoire and the number of gamma-delta T cells. They found some differences that correlated with lesion age and also found some evidence of tissue damage that did not appear to be a result of T cell activity.

Plasmacytoid dendritic cells (pDC's) in MS: Loss of interferon-alpha production after treatment with interferon-beta
Konstantin Balashov

pDC's could be the link between viral infections and relapses. pDC's produce much IFN-alpha when activated by an infection and there is a much higher level of activated pDC's in MS and thus much more IFN-alpha. In people with MS on IFN-beta, the level of IFN-alpha production was much lower, to the point of being similar to people without MS.

Incidence and clinical significance of antibodies to Tysabri over 2 years in MS
Peter Calabresi

This 2 year data on antibodies to Tysabri mirrors the 1 year data. 9-12% of people on Tysabri developed antibodies, which were persistent in 6%. People with persistent antibodies had more relapses, more disability progression, and more adverse events on the drug. Antibodies tend to be detectable within the first 12 weeks of treatment. The authors recommend that people who develop persistent antibodies discontinue use of Tysabri.

Chemokine receptor expression differentiates clinical response to interferon-beta and glatiramer acetate (Copaxone)
Samia Khoury

Brigham & Women's Hospital has an MS Registry they are creating in conjunction with Millennium Pharmaceuticals. They analyzed many characteristics of immune cells and compared the results between people on and off treatment and between responders and non-responders to interferon beta and Copaxone. So far they have found that a subtype of CD8+ cells are increased in non-responders to interferon and Copaxone, as well as in newly treated people and people with SPMS.

Clinical Outcomes (Art and Hollie)

Consensus definitions of acquired CNS demyelinating disorders of childhood
Lauren Krupp

2-5% of people with MS are less than 18 years old. A new focus on pediatric MS has caused a need to standardize on language and definitions so that research can be compared. For instance, there is confusion under current diagnostic criteria as to whether certain patients should be diagnosed with MS or ADEM. An international panel has started to meet and discuss how to diagnose younger patients with ADEM, NMO, MS, and other demyelinating diseases.

Secondary clinical progression is rare in relapsing NMO
Dean Wingerchuk

NMO (a disease similar to, but different from, MS) preferentially affects the spinal cord and optic nerve and features long lesions, severe relapses, and poor recovery. Disability in this disease has been thought only to accrue from relapses; however, there is a possibility that some disability may come about through a secondary progressive course as in MS. This team investigated the prevalence of secondary progression in NMO, and found it to exist in only 2% of subjects vs. 25% of MS subjects. This study confirms that disability in NMO is almost always related to attacks.

The relationship between NMO and systemic autoimmune disease
Brian Weinshenker

Some people with the autoimmune diseases Sjogren's syndrome or systemic lupus erythematosus (SLE) can develop optic neuritis or myelitis as well. Do these people have two distinct diseases, or are the neurological symptoms a complication of Sjogren's/SLE? Using an IgG+ marker for NMO developed at the Mayo, a team analyzed subjects with just NMO and subjects with Sjogren's/SLE, with or without NMO. They found that people without NMO did not have the antibody, whereas the Sjogren's/SLE subjects with NMO had the antibody in similar frequencies as subjects with just NMO. This suggests that NMO develops in Sjogren's/SLE subjects in the same way as it develops in just NMO subjects, making it less likely to be a complication of Sjogren's or SLE.

Evolution of benign MS in the NY State MS Consortium according to different classification criteria
Robert Zivadinov

A consortium of MS centers in NY has been collecting longitudinal data on MS patients for many years. They decided to analyze it to see if they could determine the prevalence of "benign" MS by a variety of definitions. They found about 20% of people with MS could be considered benign by a definition of EDSS

Tysabri improves health-related quality of life in patients with RRMS
Richard Rudick

Again, this was two year data on Tysabri that was similar to the one year results. This presentation discussed results from a couple of questionnaires to determine quality of life (QOL) - the MS quality of life inventory (MSQLI) and a visual analog scale.

While there were positive overall changes in QOL in subjects taking Tysabri compared to those taking placebo or Avonex alone, the investigators did not find any big effects in any particular areas (although there were a few that were statistically significant). While the results were not dramatic, this is the first time a therapy has shown any positive impact on QOL.

At this point the meeting was over and we took our booth materials over to FedEx to ship back. With tears in our eyes, we left the convention center for the last time and returned to our hotel to get dinner.

Fri 04/07:

Hollie and Julie left early in the morning. Art worked from the Hotel as he had to travel to Chicago Saturday for meetings on Sat/Sun at BIO 2006.