ALS Canada Funded Research - www.als.ca

Good news about ALS Canada funded research. Thank you to all of those who walk to support both care of PALS and research. This is why research is so important. Discovery of a new therapeutic target for ALS.
A new study -

http://jem.rupress.org/content/early/2011/11/10/jem.20111313 - was published in the November 14 online publication Journal of Experimental Medicine (JEM).
What is the study ab...out?
It is well established that inclusions of a protein called TDP-43 are a hallmark of ALS. In this study the authors report that level of TDP-43 expression is abnormally elevated in spinal cords of ALS and that this protein acts as a co-activator of nuclear factor-kappaB (NF-B) p65, which is a key protein in the signalling pathway of innate immunity (that is, our natural immediate responses against infection by pathogens).
Senior author of this paper, ALS-Canada funded researcher Jean-Pierre Julien, PhD, professor in the department of psychiatry and neuroscience at l’Université Laval – Centre de recherche du CHUQ, Quebec, believes that this new work identifies an important pathogenic pathway which has not been previously considered in TDP-43 studies from the past five years, and more importantly identifies a pathway which can be a significant therapeutic target.
Julien explains the importance of this recent discovery: “Since the discovery of TDP-43 involvement in ALS and FTD, many laboratories have searched for RNA targets of TDP-43. Unlike others, we have searched for protein targets and made the unexpected finding that TDP-43 is a binding partner of NF-Bp65. Another great surprise to me was that activation the inflammatory NF-B pathway was detected in ALS motor neurons and not only in glial cells (immune cells for the nervous system). ”
What does this mean for people living with ALS?
The good news for ALS patients is that therapeutic interventions to target this pathway are conceivable. However, we must keep in mind that NF-B inhibitors will have to be tested cautiously so as not to compromise our healthy - and necessary - immune responses. So, one of our next goals will be to develop a drug that can specifically target the interaction between TDP-43 and NF-B p65.
Why is this work exciting?
ALS Canada’s vice-president of research Denise Figlewicz, PhD, says: “This exciting new work encompasses findings from cellular, transgenic mouse, and human ALS spinal cord studies which point to a novel role for TDP-43 in the progression of ALS. What is truly significant is that the pathway and mechanisms identified here are ones for which therapeutic interventions may realistically be developed.”
What is TDP-43 and what is its role?
TDP-43 is a protein normally found in motor neurons (cells in the brain and spinal cord that control muscle movements through electrical impulses). Protein inclusions, also referred to as aggregates or clumps, are known to be present in the motor neurons of people with both the sporadic (SALS) and familial (FALS) forms of ALS. Researchers have confirmed that TDP-43 is a major component of these inclusions and that it is linked to both SALS and FALS.
The identification of TAR DNA-binding protein of 43 kilodaltons (TDP-43) in neuronal aggregates in frontotemporal lobal degeneration (FTLD) and ALS by Virginia Lee, PhD, and her colleagues at the University of Pennsylvania in 2006, was a major breakthrough in ALS research. Since then mutations in the gene encoding TDP-43 and a similar protein, fused in sarcoma (FUS) have been identified in ALS patients.
Apart from the recent discovery of mutations in the gene encoding TDP-43, the protein’s relationship to ALS is not well understood. Work from the laboratory of Michael Strong, MD, of the Robarts Research Institute in London, ON, as well as from several other laboratories, has focused on the role of TDP-43 in regulating the synthesis of specific proteins at different locations throughout the cell in response to changes in intracellular conditions. Dr. Strong is a co-author on this new publication in JEM.