title: Blockage of lysophosphatidic acid signaling improves spinal cord injury outcomes.
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.
authors: O'Brien Institute, Fitzroy, Australia.
authors: Yona
authors: Y
authors: Goldshmit
authors: Rosalia
authors: R
authors: Matteo
authors: Tamar
authors: T
authors: Sztal
authors: Felix
authors: F
authors: Ellett
authors: Frisca
authors: F
authors: Frisca
authors: Kelli
authors: K
authors: Moreno
authors: Duncan
authors: D
authors: Crombie
authors: Graham J
authors: GJ
authors: Lieschke
authors: Peter D
authors: PD
authors: Currie
authors: Roger A
authors: RA
authors: Sabbadini
authors: Alice
authors: A
authors: Pébay
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology; D008246:Lysophospholipids / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D015027:Zebrafish
chemical_list: D000911:Antibodies, Monoclonal; D008246:Lysophospholipids; D018696:Neuroprotective Agents; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid