Notes from Motor Neuron Disease Mechanisms III (Sunday November 13, 2011) at 41st SFN in Washington, DC
Thomas Philips, a PhD student in Wim Robberecht’s lab at the VIB Vesalius Research Center, K.U.Leuven in Belgium presented work on oligodendrocytes. These non-neuronal cells have only recently been a focus of ALS researchers, and their role in the disease is not entirely understood. Philips now reports that the number of oligodendrocytes present in the spinal cord significantly decreases as the ALS-like disease progresses in mice. And this decrease in oligodendrocytes was coupled with an increased proliferation and differentiation of oligodendrocyte progenitor cells (OPCs). But these efforts were insufficient to restore oligodendrocytes populations in these mice. Subsequent experiments indicated that the Notch ligand Jagged was reduced in oligodendrocytes suggesting that the notch pathway may be a therapeutic target for ALS (Philips, 2011).
From Tokai University in Tokyo, Japan, Eiichiro Nagata gave a poster presentation on experiments aimed at understanding how motor neurons degenerate in TDP43 mediated ALS.He created several HEK 293 cell lines that expressed TDP-43 and/or an inducible inositol hexakisphosphate kinase 2 (InsP6K2). Inositol hexakisphosphate kinases have been found to potential play a role in mediating cell death and similar to TDP43 and other RNA-binding proteins related to ALS disease, InsP6K2 translocates to the cytoplasm from the nucleus. And InsP6K2 according to a recent report from the Tokai University team may contribute to neuronal degeneration in Huntington’s disease. Nagata measured the level of cell death in these lines, and found that when transfected alone – neither line showed increases in apoptosis. However, when he created a line that expressed both, he found a two-fold increase in cell death. This work, according to Nagata and his colleagues, suggests that InsP6K2 may be a potential novel therapeutic target for regulating TDP43 in ALS (Nagata, 2011).
A third poster presentation during this session from Genzyme Corporation described experiments in SOD1 mice evaluating the steroid cortisol as a potential treatment strategy for ALS. This work was led by James Dodge, but reported at SFN by his colleague Jonathan Fidler. A high-powered study involving 26 male and 26 female mice in both the control and treatment groups, suggested that there may be a survival benefit upon the administration of 20 mg this steroid via subcutaneous implants over a period of 90 days. This increase in survival was only seen in the male mice (125 days in control group and 136.6 days in treatment group). There was no effect on survival observed in the female mice (Fidler, 2011).
These presentations were made at the Walter Washington Convention Center in Washington, DC. There were 31,444 people at the conference by the end of the day on Sunday. For more information about these presentations and to see a full listing of all the talks and posters made, visit www.sfn.org.
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Works Cited
Fidler, J. (2011). Alleviation of a cacostatic stress response slows disease progression in a mouse model of familial ALS. 41st Annual Meeting (p. N11). Washington, DC: Society for Neuroscience.
Nagata, E. (2011). Heat shock protein 90 (HSP90) suppresses cell death induced by cytoplasmic TDP-43 and inositol hexakisphosphate kinase 2. 41st Annual Meeting (p. N9). Washington, DC: Society for Neuroscience.
Philips, T. (2011). Oligodendrocyte lineage cells in the pathogenesis of amyotrophic lateral sclerosis. 41st Annual Meeting (p. N7). Washington, DC: Society for Neuroscience.