Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

Peter J. Crack; Moses Zhang; Maria C. Morganti-Kossmann; Andrew J. Morris; Jonathan M. Wojciak; Jonathan K. Fleming; Ila Karve; David Wright; Maithili Sashindranath; Yona Goldshmit; Alison Conquest; Maria Daglas; Leigh A. Johnston; Robert L. Medcalf; Roger A. Sabbadini; Alice Pébay

doi:10.1186/1742-2094-11-37

Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

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

Internal Medicine

Producción científica: Article › revisión exhaustiva

83 Citas (Scopus)

Resumen

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.

Idioma original	English
Número de artículo	37
Publicación	Journal of Neuroinflammation
Volumen	11
DOI	https://doi.org/10.1186/1742-2094-11-37
Estado	Published - feb 27 2014

Nota bibliográfica

Funding Information:
The authors thank Mr Duncan Crombie (Centre for Eye Research Australia and University of Melbourne) for his technical assistance. This work was supported by a National Health and Medical Research Council of Australia Project Grant 628391 (PJC), a NHMRC Career Development Award Fellowship (AP), a Transport Accident Commission project grant (AP), the ANZ Trustees Program – Medical Research & Technology in Victoria – William Buckland Foundation (AP), the United States National Institutes of Health

Funding Information:
(1R43CA132395-01A2 to RM), an Australian Research Council Future Fellowship (PJC), a University of Melbourne Collaboration Grant and the Victorian State Government’s Department of Innovation, Industry and Regional Development’s Operational Infrastructure Support Program.

Funding Information:
PJC, RAS and AP conceived the experiments. MZ, IK, MS, RLM, and MD performed TBI experiments and behavioral analysis. YG performed immunochemistry. MZ, DW and LAJ performed MRI experiments. RAS developed the anti-LPA mAbs. ACMK and AC collected CSF samples. AM and JMW performed HPLC MS measurements. JKF and JMW performed the KinExA assays. All authors contributed to data analysis and writing of the manuscript. PJC, RAS, and AP contributed financial support for this work. All authors have read and approved the final version of the manuscript.

Financiación

The authors thank Mr Duncan Crombie (Centre for Eye Research Australia and University of Melbourne) for his technical assistance. This work was supported by a National Health and Medical Research Council of Australia Project Grant 628391 (PJC), a NHMRC Career Development Award Fellowship (AP), a Transport Accident Commission project grant (AP), the ANZ Trustees Program – Medical Research & Technology in Victoria – William Buckland Foundation (AP), the United States National Institutes of Health (1R43CA132395-01A2 to RM), an Australian Research Council Future Fellowship (PJC), a University of Melbourne Collaboration Grant and the Victorian State Government’s Department of Innovation, Industry and Regional Development’s Operational Infrastructure Support Program. PJC, RAS and AP conceived the experiments. MZ, IK, MS, RLM, and MD performed TBI experiments and behavioral analysis. YG performed immunochemistry. MZ, DW and LAJ performed MRI experiments. RAS developed the anti-LPA mAbs. ACMK and AC collected CSF samples. AM and JMW performed HPLC MS measurements. JKF and JMW performed the KinExA assays. All authors contributed to data analysis and writing of the manuscript. PJC, RAS, and AP contributed financial support for this work. All authors have read and approved the final version of the manuscript.

Financiadores	Número del financiador
ANZ Trustees Program
Medical Research & Technology in Victoria
University of Melbourne Collaboration
Victorian State Government’s Department of Innovation, Industry and Regional Development’s
William Buckland Foundation
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute	R43CA132395
National Childhood Cancer Registry – National Cancer Institute
Australian Research Council
Australian National Health and Medical Research Council	628391
Australian National Health and Medical Research Council
Transport Accident Commission
Russian Academy of Sciences

ASJC Scopus subject areas

General Neuroscience
Immunology
Neurology
Cellular and Molecular Neuroscience

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10.1186/1742-2094-11-37

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Crack, P. J., Zhang, M., Morganti-Kossmann, M. C., Morris, A. J., Wojciak, J. M., Fleming, J. K., Karve, I., Wright, D., Sashindranath, M., Goldshmit, Y., Conquest, A., Daglas, M., Johnston, L. A., Medcalf, R. L., Sabbadini, R. A., & Pébay, A. (2014). Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes. Journal of Neuroinflammation, 11, Artículo 37. https://doi.org/10.1186/1742-2094-11-37

@article{3b658cb24abd46949b21b57d87dfa0a8,

title = "Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes",

abstract = "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.",

keywords = "Anti-LPA antibody, Control cortical impact, Human cerebrospinal fluid, IL-6, Lysophosphatidic acid, Magnetic resonance imaging, Traumatic brain injury",

author = "Crack, \{Peter J.\} and Moses Zhang and Morganti-Kossmann, \{Maria C.\} and Morris, \{Andrew J.\} and Wojciak, \{Jonathan M.\} and Fleming, \{Jonathan K.\} and Ila Karve and David Wright and Maithili Sashindranath and Yona Goldshmit and Alison Conquest and Maria Daglas and Johnston, \{Leigh A.\} and Medcalf, \{Robert L.\} and Sabbadini, \{Roger A.\} and Alice P{\'e}bay",

note = "Funding Information: The authors thank Mr Duncan Crombie (Centre for Eye Research Australia and University of Melbourne) for his technical assistance. This work was supported by a National Health and Medical Research Council of Australia Project Grant 628391 (PJC), a NHMRC Career Development Award Fellowship (AP), a Transport Accident Commission project grant (AP), the ANZ Trustees Program – Medical Research \& Technology in Victoria – William Buckland Foundation (AP), the United States National Institutes of Health Funding Information: (1R43CA132395-01A2 to RM), an Australian Research Council Future Fellowship (PJC), a University of Melbourne Collaboration Grant and the Victorian State Government{\textquoteright}s Department of Innovation, Industry and Regional Development{\textquoteright}s Operational Infrastructure Support Program. Funding Information: PJC, RAS and AP conceived the experiments. MZ, IK, MS, RLM, and MD performed TBI experiments and behavioral analysis. YG performed immunochemistry. MZ, DW and LAJ performed MRI experiments. RAS developed the anti-LPA mAbs. ACMK and AC collected CSF samples. AM and JMW performed HPLC MS measurements. JKF and JMW performed the KinExA assays. All authors contributed to data analysis and writing of the manuscript. PJC, RAS, and AP contributed financial support for this work. All authors have read and approved the final version of the manuscript.",

year = "2014",

month = feb,

day = "27",

doi = "10.1186/1742-2094-11-37",

language = "English",

volume = "11",

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Crack, PJ, Zhang, M, Morganti-Kossmann, MC, Morris, AJ, Wojciak, JM, Fleming, JK, Karve, I, Wright, D, Sashindranath, M, Goldshmit, Y, Conquest, A, Daglas, M, Johnston, LA, Medcalf, RL, Sabbadini, RA & Pébay, A 2014, 'Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes', Journal of Neuroinflammation, vol. 11, 37. https://doi.org/10.1186/1742-2094-11-37

TY - JOUR

T1 - Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

AU - Crack, Peter J.

AU - Zhang, Moses

AU - Morganti-Kossmann, Maria C.

AU - Morris, Andrew J.

AU - Wojciak, Jonathan M.

AU - Fleming, Jonathan K.

AU - Karve, Ila

AU - Wright, David

AU - Sashindranath, Maithili

AU - Goldshmit, Yona

AU - Conquest, Alison

AU - Daglas, Maria

AU - Johnston, Leigh A.

AU - Medcalf, Robert L.

AU - Sabbadini, Roger A.

AU - Pébay, Alice

N1 - Funding Information: The authors thank Mr Duncan Crombie (Centre for Eye Research Australia and University of Melbourne) for his technical assistance. This work was supported by a National Health and Medical Research Council of Australia Project Grant 628391 (PJC), a NHMRC Career Development Award Fellowship (AP), a Transport Accident Commission project grant (AP), the ANZ Trustees Program – Medical Research & Technology in Victoria – William Buckland Foundation (AP), the United States National Institutes of Health Funding Information: (1R43CA132395-01A2 to RM), an Australian Research Council Future Fellowship (PJC), a University of Melbourne Collaboration Grant and the Victorian State Government’s Department of Innovation, Industry and Regional Development’s Operational Infrastructure Support Program. Funding Information: PJC, RAS and AP conceived the experiments. MZ, IK, MS, RLM, and MD performed TBI experiments and behavioral analysis. YG performed immunochemistry. MZ, DW and LAJ performed MRI experiments. RAS developed the anti-LPA mAbs. ACMK and AC collected CSF samples. AM and JMW performed HPLC MS measurements. JKF and JMW performed the KinExA assays. All authors contributed to data analysis and writing of the manuscript. PJC, RAS, and AP contributed financial support for this work. All authors have read and approved the final version of the manuscript.

PY - 2014/2/27

Y1 - 2014/2/27

N2 - 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.

AB - 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.

KW - Anti-LPA antibody

KW - Control cortical impact

KW - Human cerebrospinal fluid

KW - IL-6

KW - Lysophosphatidic acid

KW - Magnetic resonance imaging

KW - Traumatic brain injury

UR - https://www.scopus.com/pages/publications/84899476317

UR - https://www.scopus.com/pages/publications/84899476317#tab=citedBy

U2 - 10.1186/1742-2094-11-37

DO - 10.1186/1742-2094-11-37

M3 - Article

C2 - 24576351

AN - SCOPUS:84899476317

SN - 1742-2094

VL - 11

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

M1 - 37

ER -

Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

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