TY - JOUR
T1 - Blockage of lysophosphatidic acid signaling improves spinal cord injury outcomes
AU - Goldshmit, Yona
AU - Matteo, Rosalia
AU - Sztal, Tamar E
AU - Ellett, Felix
AU - Frisca, Frisca
AU - Moreno, Kelli
AU - Crombie, Duncan
AU - Lieschke, Graham J
AU - Currie, Peter D
AU - Sabbadini, Roger A
AU - Pebay, Alice
PY - 2012
Y1 - 2012
N2 - Evidence suggests a proinflammatory role of lysophosphatidic acid (LPA) in various pathologic abnormalities, including in the central nervous system. Herein, we describe LPA as an important mediator of inflammation after spinal cord injury (SCI) in zebrafish and mice. Furthermore, we describe a novel monoclonal blocking antibody raised against LPA that potently inhibits LPA s effect in vitro and in vivo. This antibody, B3, specifically binds LPA, prevents it from interacting with its complement of receptors, and blocks LPA s effects on the neuronal differentiation of human neural stem/progenitor cells, demonstrating its specificity toward LPA signaling. When administered systemically to mice subjected to SCI, B3 substantially reduced glial inflammation and neuronal death. B3-treated animals demonstrated significantly more neuronal survival upstream of the lesion site, with some functional improvement. This study describes the use of anti-LPA monoclonal antibody as a novel therapeutic approach for the treatment of SCI.
AB - Evidence suggests a proinflammatory role of lysophosphatidic acid (LPA) in various pathologic abnormalities, including in the central nervous system. Herein, we describe LPA as an important mediator of inflammation after spinal cord injury (SCI) in zebrafish and mice. Furthermore, we describe a novel monoclonal blocking antibody raised against LPA that potently inhibits LPA s effect in vitro and in vivo. This antibody, B3, specifically binds LPA, prevents it from interacting with its complement of receptors, and blocks LPA s effects on the neuronal differentiation of human neural stem/progenitor cells, demonstrating its specificity toward LPA signaling. When administered systemically to mice subjected to SCI, B3 substantially reduced glial inflammation and neuronal death. B3-treated animals demonstrated significantly more neuronal survival upstream of the lesion site, with some functional improvement. This study describes the use of anti-LPA monoclonal antibody as a novel therapeutic approach for the treatment of SCI.
UR - http://www.sciencedirect.com/science/article/pii/S0002944012004440#
U2 - 10.1016/j.ajpath.2012.06.007
DO - 10.1016/j.ajpath.2012.06.007
M3 - Article
SN - 0002-9440
VL - 181
SP - 978
EP - 992
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -