Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

Peter J Crack, Moses Zhang, Maria Cristina Morganti-Kossmann, Andrew Morris, Jonathan M Wojciak, Jonathan K Fleming, Ila Karve, David K Wright, Maithili Sashindranath, Yona Goldshmit, Alison Conquest, Maria Daglas, Leigh Andrea Johnston, Robert Lindsay Medcalf, Roger A Sabbadini, Alice Pebay

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Background: Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury. FINDINGS: Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes. Conclusions: This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction.
Original languageEnglish
Pages (from-to)1 - 11
Number of pages11
JournalJournal of Neuroinflammation
Issue number(Art. No: 37)
Publication statusPublished - 2014

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