Following the conclusion of each day during the SFN meeting, our Director of Communications (Rob), will publish his thoughts on posters and presentations which he attended. There are thousands of such events each day at the meeting, which was held in San Diego this year. Rob’s viewpoints and opinions are his own and nothing below is meant to replace the advice a person receives from their personal medical team. You can email ALS TDI directly at marketing@als.net with questions or comments on his recaps. Discussion on these notes and the meeting, in general, is taking place at the ALS Forum located here: www.als.net/forum
Wednesday, my last day in San Diego, and likely the biggest ALS research day of the annual meeting this year. There were nearly two entire aisle’s filled with posters presenting innovative science, preclinical and clinic results pertaining to ALS and my notes that follow encompass those which I felt to be most interesting. I should point out that pretty much every major laboratory working on ALS in the world had representatives at the meeting today, as well as the science directors from major funding organizations in the ALS including the MDA, ALSA and the NIH. The mix of people in the aisles was a venerable who’s who of ALS research, but honestly, there was one person missing – the ALS patient. I am really hopeful that we will be able to include those living with ALS (and other neurodegenerative diseases) in this event in the future and I hope that will be the case in Washington, DC when SFN is held there next year. While this is certainly a “hardcore” science meeting, I don’t think that we can ever miss an opportunity to put patients today first in the minds of researchers and this venue presents a unique opportunity to do just that. But that’s just my opinion.
One of the first posters I saw was from the Royal College of Surgeons in Ireland, who reported their results from a preclinical investigation of angiogenin in the SOD1G93A mouse (Behan, 2010). On average, the group showed a statistically significant improvement in survival in their study which was done in 24 mice, half dosed with the protein starting at 90 days. In speaking with the group at the poster, they reported that they would like to continue their research and try increasing the dose to attempt to determine the optimal dose of protein and to establish a dose response to the protein on disease progression.
With the next several posters over-run with neuro-nerds, I took a stroll down to see results from an investigation targeting AMP-activated protein kinase in the mouse model (Lomas, 2010). Her goal was to upregulate FGC-1 with is downstream from AMPK. In this presentation, the researcher chose to attempt to target that pathways using metforim, a well known anti-diabetic drug which has been reported to hit that target. In carrying out her experiment, she dosed animals with three different doses (.5 mg/kg, 2 mg/kg and 5 mg/kg). However, the dosing strategy didn’t pan out and there was no effect of survival overall, however there may have been a slight gender related effect, similar to that reported by ALS TDI when it published its own metformin data earlier last year. Metformin was selected by the ALS Forum for testing at ALS TDI in 2009.
In the same area was an interesting poster presentation on a substance called MitQ, which is designed to increase mitochondrial activity. The researchers also showed data which seemed to show that the drug prevented astrocytes toxicity in muscle and spinal cord samples collected from the mice. The animal study, which was done unfortunately in an underpowered way with only 4 males and 5 female mice, the researchers claimed that the drug delayed onset of disease and extended survival by several days (Cassina, 2010).
Similar research was also reported on the testing of the female hormone producing drug, progesterone (Kim, 2010). Researchers in that study showed that motor neurons were more likely to survive when they received the treatment, however the animal experiment was not gender matched according the representative from the group that was manning the poster when I got over there. I am going to skip comments on BuNaoGao (BNG), because I didn’t get a chance to speak to the researcher myself, however there were several spirited discussions that seemed to be taking place near that poster (Xia, 2010). At the other end of the aisle were Dr. Svendsen’s lab’s results from the transplantation of cells that express of GDNP into the cervical cord of mine (Gowing, 2010). It was really quite remarkable work which showed that implants of this type could also help to strengthen phrenic motor output (Nichols, 2010). That specific nerve is one of the primary controllers of the diaphragm, which is the crucial muscle involved in the regulation of breathing.
On the clinical side of things, I was able to spend a few moments with the representations from Sangamo Biosciences, which is a private company that recently conducted a Phase II Clinical Trial on SB-509 in ALS patients. SB-509 is designed to up-regulate the endogenous VEGF-A gene. VEGF stands for vascular endothelial growth factor, and it’s important to note that researchers in ALS have been very interested in testing various forms of growth factors. This is a very high-profile trial (as most ALS trials are because there is such a dire need) and many ALS Forum members requested that I go see this poster and speaker with the folks at the presentation of it. In all, there were 45 patients in the trial, with 39 of them getting injections of the protein (a derivative of vascular endothelial growth factor (VEGF)) at various sites in the body, including the intramuscular injections in the arms, legs and area around the spinal cord. The other cohort received intramuscular injections only in the legs. This was done for a couple of reasons, but primarily to see if the researchers could determine a localized response and to allow the company to compare the results from this study to results from their study of the use of this drug in patients with diabetic neuropathy, which were only getting the treatment in the legs. In the ALS study, I thought it was really quite wise that they measured (and reported) progression via the ALSFRS (functional rating scale), FVC (force vital capacity) and MMT (manual muscle test). The results from the study reported were preliminary, but the researchers presenting the data showed results that claimed that muscle strength improved during the phase II trial. They also showed initial data that connected the improvement of muscle strength to the expression signaling connected to their treatment in areas where it was delivered. In essence, the density of the treatment seemed to correlate with the outcome. The researchers are planning, as I said, to move forward (based on final analysis obviously) into the next phase of clinical trial for ALS only after they complete analysis of this data and their other trial on this drug (which is their primary trial for this drug by the way) is completed (Benaim, 2010).
During the afternoon, I attended yet another packed poster session on ALS. There were two posters in this session that I found interesting (I’m sure my colleagues saw others that they would add). First, there was an interesting poster on axonal transport, which showed that there is an apparent deficit of mitochondria as early as day 20 in the SOD1G93A mouse. This is well before disease onset (day 70), so I certainly could my eye. There has been an increased focus on mitochondria activity/efficiency in ALS over the past couple of years so I thought this was a great poster aimed at helping to establish some of the theory around why it could provide to be an interesting observation to target (Mitchell, 2010). The other poster that I saw during the afternoon which interested me posted U3, which again focused on trying to establish a link between an observation and disease outcome. This research project described how a decrease in calreticulin (a binding protein to calcium ions) is upstream to stress on a cell’s ER (endoplasmic reticulum), which in turn has been shown to be a potentially important pathway that leads to motor neuron death. The researcher’s project aimed to show that regulating calreticulin could regular ER stress, hence protect motor neurons (Bernard, 2010).
There were lots of other posters and presentations which I saw in San Diego and believe me, my colleagues saw a lot more as well! I will be happy to post notes from my colleagues Dr. Perrin, Lincecum and DeZutter for folks on any topic that they may have found interesting that was listed as having taken place at SFN this year. Please just let me know. As a final comment, I would like to thank Jet Blue for the free DirectTV on the fly home, so I could watch one of the greatest advocates for ALS research in Washington, Sen. Lisa Murkowski, announce that she would in fact be reelected. O yeah, and the fact that they serve Dunkin Donuts coffee on that airline helps too, although I probably shouldn’t have drank so much coffee at the start of the red-eye. Thank you all for reading these updates, I hope they were useful. I will be providing recaps (from my POV) from the Annual International ALS/MND Research Symposium being held this December in Orlando Florida. Until then….
Works Cited
Behan, A. T. (2010). Systemic delivery of angiogenin protein for the treatment of ALS. Royal College of Surgeons in Ireland. Dublin, Ireland: Society for Neurscience 40th Annual Meeting.
Benaim, E., et.al. (2010). Plasmid gene transfer of zinc finger protein vegf-a transcription activator (SB-509) for treatment of amytrophic lateral sclerosis (als) - a phase 2 clinical trial. Sangamo BioSciences, Inc. Richmond, CA, USA: Society for Neuroscience 40th Annual Meeting.
Bernard, N., et.al. (2010). Calrecticulin: A link between ER stress and death in SOD1-associated ALS motorneurons. INMED. Marseille Cedex 09, France: Society for Neuroscience 40th Annual Meeting.
Cassina, M., et.al. (2010). The mitochondria-targeted antioxidant MitoQ improves survival in the SOD G93A mouse model of ALS. Universidad de la República, Facultad de Medicina. Montevideo, Uruguay: Society for Neuroscience 40th Annual Meeting.
Gowing, G., et.al. (2010). Targeting of human neural progenitor cells expressing GDNF to the cervical spinal cord of a rat model of ALS. Cedar-Siani Medical Center, Regenerative Medicine Institute. Los Angeles, CA, USA: Society for Neuroscience.
Kim, J., et.al. (2010). Progesterone delays disease progression and increases survival of G93A SOD-1 transgenic mice. Ulsan College. Seoul, Republic of South Korea: Society for Neuroscience 40th Annual Meeting.
Lomas, H., et.al. (2010). Targeting AMP-activated protein kinase as a therapeutic strategy for Amyotrophic Lateral Sclerosis. Imperial College London, Centre. for Neuroscience, Department of Experimental Medicine and Toxicology. London, England, UK: Society for Neuroscience 40th Annual Meeting.
Mitchell, C., et.al. (2010). Cargo distributions differentiate motorneuron axonal transport impairment mechanisms in ALS. Georgia Institute of Technology, Department of Biomedical Engineering. Atlanta, GA, USA: Society for Neuroscience.
Nichols, N., et.al. (2010). GDNF-secreting neural progenitor cell implants strengthen phrenic motor output in a rodent model of ALS (SOD1G93A rats). university of Wisconsin, Dept Computational Biology. Madison, WI, USA: Society for Neuroscience.
Xia, M., et.al. (2010). Improved survival among western als patients using bunaogao (bng), March 2003-March 2010. TianHe Bioscience, Inc. Lexington, MA, USA: Society for Neuroscience 40th Annual Meeting.
To read abstracts cited, please visit www.sfn.org/am2010 and click on “Neuroscience Meeting Planner” then search by author last name. That should be the quickest route.