Blockage of lysophosphatidic acid signaling improves spinal cord injury outcomes

Yona Goldshmit, Rosalia Matteo, Tamar E Sztal, Felix Ellett, Frisca Frisca, Kelli Moreno, Duncan Crombie, Graham J Lieschke, Peter D Currie, Roger A Sabbadini, Alice Pebay

Research output: Contribution to journalArticleResearchpeer-review

41 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)978 - 992
Number of pages15
JournalAmerican Journal of Pathology
Volume181
Issue number3
DOIs
Publication statusPublished - 2012

Cite this