May 7, 2004
Boston Cure Project
During the last week of April, Art and Hollie flew out to San Francisco to attend the annual meeting for the American Academy of Neurology (AAN). At this meeting many of the top MS researchers come together and present their work. Below are some notes I took on my visit there. Hollie will follow up with additional notes of her own.
Art's Boston Cure Project trip report for AAN mtg in San Francisco, April 2004
Fri 04/24/04 - Sun 04/25/04:
Art & Debbie flew out the weekend before to meet up with friends and enjoy San Francisco a bit. They were having a heat wave with temperatures in the 90's (compared with Boston's rainy 40-50's).
Debbie flew out, Art went to meet with a potential supporter in San Jose. Hollie flew in and she and Art drove down to Saratoga to meet with Scott Johnson and Rusty Bromley of the Myelin Repair Foundation (http://www.myelinrepair.org). This is another small start-up nonprofit, started by an engineer diagnosed with MS, and is focused on, surprise, surprise, the repair of myelin. Their genesis, philosophy, and attitude mirrors that of the Boston Cure Project to an uncanny level. A really good group to keep an eye on.
We went and attended the morning Poster sessions where researchers put up posters describing their latest research and are often standing next to them so you can ask questions. We didn't see anything earth-shattering in this session.
Attended the Plenary session in the morning. Most of the talks were non-MS related, but one by William Mobley covered neurotrophic factors and how they might signal from the axon terminal to the cell body to keep the axon alive. He presented evidence of some new organelles he called signalling endosomes that physically move the chemical signal from the axon terminal to the cell body to communicate that it has a valid target. Axons that don't find their targets die.
During the lunch break we attended the exhibit hall that has booths with representatives from pharma, biotech, medical device, and nonprofit organizations. We ran into a number of people we knew and met some new ones. We saw people at Teva, Berlex, Biogen, and Serono and made some connections with the MSAA, Betaseron Foundation, and Corielle (a nonprofit tissue banking organization).
At this point I went to the Clinical Trials track of MS presentations and Hollie went to the imaging track. It was standing room only in the Clinical Trials room. Again, there wasn't anything too exciting to hear about. My take on the presentations is as follows.
A Copaxone trial in Primary Progressive MS (PROMiSE) presented its results which were poor. It seems they could not determine that there was any benefit at all. Needed to be longer and include more people to see any effect at all.
Daclizumab (an IL-2 receptor antibody, also called Zenapax) reduced MRI results somewhat in people with relapsing remitting and secondary progressive. About half the subjects seemed to respond and half were stable over 5-25 mos in the trial. Probably needs to be done for longer.
Samia Khoury from the Brigham presented some very preliminary data on CTLA4Ig. They have infused 8 (of 16) people so far and found that there have been no serious adverse events and that there seems to be some bio-effect, but no data on efficacy is available.
A Phase 2 Mitoxantrone in Primary Progressive MS, given every 3 months over 2 years showed no significant effects.
An oral drug called Laquinimod taken daily for 24 weeks in 187 subjects seems to reduce active lesion count. A longer trial is needed.
In the next session, Larry Steinman of Stanford was presented with the Dystel Award by the AAN and NMSS. Basically its to acknowledge the value of his contributions and give him some cash to go party with.
Larry gave a quick talk reviewing a number of new target pathways that are being looked at including Altered Peptide Ligands, DNA Vaccines, Antegren, Statins, and Anti-Histamines.
A study testing the effects of Donepezil on memory and cognition showed minor (10%) improvement in verbal memory performance.
Ken Johnson presented data from the ongoing tracking of the original Copaxone study group. It seems that those who have stayed on Copaxone for the past 10 years have done better than those who did not. But this neglects the fact that if you aren't doing well on it, you'll probably stop. I guess we can conclude that there are some people who respond to Copaxone and the drug can be tolerated by some for 10 years.
Another talk on treating pregnancy related relpases with steroids showed a significant reduction in relapses in the first trimester post birth when taking solumedrol shortly after giving birth and then monthly thereafter for 6 months.
After the presentations we ran into Stephen Reingold, the VP of Research at the NMSS, who didn't react well when he found out who I was (oh well). We also heard (separately) that he has announced his early retirement in Jan 2005.
That evening Hollie and I went to dinner with Jorge Oksenberg (one of our Scientific Advisors who has helped tremendously with the genetics component of the cure map) and his wife Donna.
Went and checked out the poster sessions in the morning and then went to meet with Larry Steinman from Stanford. He liked what we are working on and agreed to join our Scientific Advisory Board.
We caught the end of the plenary session and saw Stephan Hauser give a talk on current developments in MS. He talked about anti-MOG and anti-MBP antibodies as a diagnostic tool. EAE in marmosets as a better animal model, and work on gene expression signature tool they are working on to be an indicator of Interferon response.
We then had lunch with Ursala Utz from the NIH. She knows everything that's going on and everyone doing it. She lamented how tight NIH funding was the past couple of years for MS. However, she did mention a big combination therapy trial they are funding to look into the benefits of doing both Avonex and Copaxone together.
The first afternoon session for the MS track was so over subscribed that I had to sit out in the hallway and only listen. It's hard to get much from the talks that way. The second session was less attended so we got to hear better, but none of the talks revealed any breakthroughs. Rip Kinkel's talk on the continuing results of the CHAMPIONS trial (Avonex) was at least interesting and well presented.
At the end of the session we went to talk to one of the chairs, Amit Bar-Orr from Canada. We'll be talking to him later some more to see if he'd like to join our scientific advisory board.
I stayed at the hotel doing some work during the morning plenary. The rest of the day was similar to previous days, seeing a number of presentations on imaging and immunology this time. Again, nothing very earthshattering, although Dr. Freedman presented some results from 3 MS subjects who have undergone a complete immune system "reboot" which seems to have stabilized their (previously rapidly declining) disease over the past couple of years.
I also managed to meet some more folks from a variety of places like the Brigham, Biogen Idec, and the Cleveland Clinic.
For dinner we met with some more potential supporters
Worked from the hotel until we had to fly out. Got back to Boston uneventfully.
Additional notes from Hollie:
Art has covered the meeting quite thoroughly but I have a few notes to add from the sessions I attended. Most of them have to do with imaging, which is becoming quite a hotbed of research in the study of MS these days (and which I'm personally very interested in!).
A session Tuesday afternoon featured several talks having to do with the measurement of brain atrophy in MS. Elizabeth Fisher reported that brain atrophy in relapsing remitting MS (RRMS) was related to the presence of focal lesions but not diffuse damage in normal appearing brain matter. However, the opposite appears to be true in secondary progressive MS (SPMS) indicating different mechanisms at work in these two stages of MS. Michela Tiberio also found that white matter atrophy was related to the presence of inflammatory lesions in early RRMS but that gray matter atrophy appears to be even more significant than white matter atrophy in the early stages of the disease. Bernhard Sturm reported on a technique for measuring atrophy in specific sections of the brain which seems like a sensible approach to understanding the variability in the clinical aspects of MS. He and his team are already finding significant variations in the location and degree of regional atrophy among the subjects they have studied.
In a plenary session talk Thursday morning, Richard Ransohoff of the Cleveland Clinic gave a good overview of the role of chemokines and chemokine receptors in neurological systems. Chemokines help to regulate and activate various components of the immune system. Although most of the talk was not MS-specific, Ransohoff did mention that CCR1 antagonists are currently being investigated as a possible MS treatment, and that CXCL1 which stops oligodendrocyte precursor migration is produced by astrocytes at the border of MS lesions and may be preventing the entry of new oligo's into lesions.
Another imaging panel on Thursday afternoon included some presentations about novel techniques for studying MS disease and repair activity. Daniel Pelletier reported on a technique for distinguishing glutamate in the brain (increased glutamate is associated with axonal and oligodendrocyte damage), as well as myo-inositol which is a marker of glial cells. Elizabeth Murphy discussed a way to image myelin formation through the ingestion of heavy water, which is incorporated into GalC, which is a major component of myelin. Being able to image myelination is going to be essential for measuring the efficacy of myelin restorative therapies when we have them. Finally, a Dr. Fernando presented findings from an imaging study of subjects in the earliest stages of MS ("clinically isolated syndromes" or initial MS symptoms). He and his team found little evidence for axonal loss in the normal appearing white matter in this stage of MS; however, an increase in myo-inositol was detected, indicating a proliferation of glial cells. Further studies of this nature will help add to our knowledge of the earliest events in MS.
Next year's AAN will be in Miami Beach from April 9-16. It has a large
MS focus, so anyone who is up on the medical and technical jargon and wants
to hear the latest research news directly from MS scientists might think
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