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Exp Neurol. 2015 Jul;269:154-68. doi: 10.1016/j.expneurol.2015.04.008. Epub 2015 Apr 19.

Large animal and primate models of spinal cord injury for the testing of novel therapies.

Author information

1
University of British Columbia, ICORD, Room 6196, Blusson Spinal Cord Centre, 818 West 10th Avenue, Vancouver, BC V5Z 1 M9, Canada. Electronic address: brian.kwon@ubc.ca.
2
University of British Columbia, ICORD, Room 6196, Blusson Spinal Cord Centre, 818 West 10th Avenue, Vancouver, BC V5Z 1 M9, Canada. Electronic address: femkestreijger@gmail.com.
3
Burke Medical Research Institute/Weill Cornell Medical College, 785 Mamaroneck Ave., White Plains, NY 10605, USA. Electronic address: cah2024@med.cornell.edu.
4
U. C. Irvine, 2030 Gross Hall Stem Cell Research Center, USA. Electronic address: aja@uci.edu.
5
International Spinal Research Trust, International Spinal Research Trust, Bramley Business Centre, Station Road, Bramley, Guildford, Surrey GU5 0AZ, UK. Electronic address: mark@spinal-research.org.
6
University of California at San Francisco, 1001 Potrero Ave., Bldg 1 Rm 101, San Francisco, CA 94110, USA. Electronic address: Michael.beattie@ucsf.edu.
7
Heidelberg University Hospital, Spinal Cord Injury Center, Germany. Electronic address: armin.blesch@med.uni-heidelberg.de.
8
King's College London, The Wolfson Centre for Age-Related Diseases, Wolfson Wing, Hodgkin Building, Guy's Campus, London Bridge, London SE1 1UL, UK. Electronic address: elizabeth.bradbury@kcl.ac.uk.
9
University of Western Ontario, Robarts Research Institute, University of Western Ontario, Department of Anatomy and Cell Biology, 1151 Richmond Street, North, N6A 5B7, Canada. Electronic address: abrown@robarts.ca.
10
University of California at San Francisco, 1001 Potrero Ave., Bldg 1 Rm 101, San Francisco, CA 94110, USA. Electronic address: Jacqueline.bresnahan@ucsf.edu.
11
Asterias Biotherapeutics, 230 Constitution Drive, Menlo Park, CA 94025, USA. Electronic address: ccase@asteriasbio.com.
12
Acorda Therapeutics, Acorda Therapeutics, Inc., 420 Saw Mill River Road, Ardsley, NY 10502, USA. Electronic address: rcolburn@acorda.com.
13
Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, 1650 Cedar Ave., Montreal, Quebec H3G 1A4, Canada. Electronic address: sam.david@mcgill.ca.
14
University of Cambridge, John van Geest Centre for Brain Repair, Robinson Way, Cambridge CB2 0PY, UK. Electronic address: jf108@cam.ac.uk.
15
University of California, San Francisco (UCSF), Brain and Spinal Injury Center (BASIC), Department of Neurological Surgery, USA. Electronic address: Adam.ferguson@ucsf.edu.
16
Drexel University College of Medicine, Dept. of Neurobiology and Anatomy, 2900 Queen Lane, Philadelphia, PA 19129, USA. Electronic address: Itzhak.Fischer@DrexelMed.edu.
17
University of Alabama at Birmingham, 529C Spain Rehabilitation Center, 1717 6th Avenue South, Birmingham, AL 35249, USA. Electronic address: clfloyd@uab.edu.
18
University of Kentucky, Spinal Cord and Brain Injury Research Center, B463 Biomedical & Biological Sciences Research Building (BBSRB), 741 S. Limestone, Lexington, KY 40536, USA. Electronic address: Gensel.1@uky.edu.
19
Drexel University College of Medicine, Spinal Cord Research Center, Philadelphia, PA 19129, USA. Electronic address: jhoule@drexelmed.edu.
20
National Institutes of Health/NINDS, 6001 Executive Blvd. North, Bethesda, MD 20852, USA. Electronic address: lyn.jakeman@nih.gov.
21
Iowa State University, Lloyd Veterinary Medical Center, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. Electronic address: njeffery@iastate.edu.
22
Craig H. Neilsen Foundation, 16830 Ventura Blvd. Suite 352, Encino, CA 91436, USA. Electronic address: linda@chnfoundation.org.
23
Craig H. Neilsen Foundation, 16830 Ventura Blvd. Suite 352, Encino, CA 91436, USA. Electronic address: naomi@chnfoundation.org.
24
Yale University and VA CT Healthcare System, Neuroscience Center (127A), VA CT Healthcare Center, 950 Campbell Ave., West Haven, CT 06516, USA. Electronic address: Jeffery.kocsis@yale.edu.
25
VA-San Diego Healthcare System, University of California at San Diego, BMF2, Room 2126, 9500 Gilman Dr., La Jolla, CA 92093-0626, USA. Electronic address: plu@ucsd.edu.
26
University of Louisville School of Medicine, 511 S. Floyd St., MDR Rm 616, USA. Electronic address: david.magnuson@louisville.edu.
27
University of California, San Diego, Department of Anesthesiology SCRM, Room 4009, 2880 Torrey Pines Scenic Dr., La Jolla, CA 92037, USA. Electronic address: mmarsala@ucsd.edu.
28
InVivo Therapeutics Corporation, One Kendall Square, Suite B14402, Cambridge, MA 02139, USA. Electronic address: smoore@invivotherapeutics.com.
29
Toronto Western Research Institute, Krembil Discovery Tower, 60 Leonard Ave. , 7KD-406, Toronto ON M5T 2S8, Canada. Electronic address: amothe@uhnres.utoronto.ca.
30
University of Miami Miller School of Medicine, LPLC, 1095 NW 14 Terrace, Miami, FL 33136, USA. Electronic address: moudega@pitt.edu.
31
Stanford University, Lorry I. Lokey Stem Cell Research Building, Stanford University, 265 Campus Drive, Stanford, CA 94305, USA. Electronic address: gplant@stanford.edu.
32
University of Kentucky, B471, BBSRB, 741 South Limestone Street, Lexington, KY 40536-0509, USA. Electronic address: agrab@uky.edu.
33
The Ohio State University, Neurology, USA. Electronic address: jan.schwab@osumc.edu.
34
Case Western Reserve University, Dept. of Neurosciences, School of Medicine, 2109 Adelbert Rd., Cleveland, OH 44106, USA. Electronic address: jxs10@case.edu.
35
University of California Irvine, Reeve-Irvine Research Center, Department of Anatomy & Neurobiology, University of California Irvine School of Medicine, Irvine, CA 92697, USA. Electronic address: osteward@uci.edu.
36
Indiana University School of Medicine, 320 W. 15th St., Indianapolis, IN 46202, USA. Electronic address: Xu26@iupui.edu.
37
University of Miami, Neurological Surgery, USA. Electronic address: jguest@med.miami.edu.
38
University of British Columbia, ICORD, Room 6196, Blusson Spinal Cord Centre, 818 West 10th Avenue, Vancouver, BC V5Z 1 M9, Canada. Electronic address: tetzlaff@icord.org.

Abstract

Large animal and primate models of spinal cord injury (SCI) are being increasingly utilized for the testing of novel therapies. While these represent intermediary animal species between rodents and humans and offer the opportunity to pose unique research questions prior to clinical trials, the role that such large animal and primate models should play in the translational pipeline is unclear. In this initiative we engaged members of the SCI research community in a questionnaire and round-table focus group discussion around the use of such models. Forty-one SCI researchers from academia, industry, and granting agencies were asked to complete a questionnaire about their opinion regarding the use of large animal and primate models in the context of testing novel therapeutics. The questions centered around how large animal and primate models of SCI would be best utilized in the spectrum of preclinical testing, and how much testing in rodent models was warranted before employing these models. Further questions were posed at a focus group meeting attended by the respondents. The group generally felt that large animal and primate models of SCI serve a potentially useful role in the translational pipeline for novel therapies, and that the rational use of these models would depend on the type of therapy and specific research question being addressed. While testing within these models should not be mandatory, the detection of beneficial effects using these models lends additional support for translating a therapy to humans. These models provides an opportunity to evaluate and refine surgical procedures prior to use in humans, and safety and bio-distribution in a spinal cord more similar in size and anatomy to that of humans. Our results reveal that while many feel that these models are valuable in the testing of novel therapies, important questions remain unanswered about how they should be used and how data derived from them should be interpreted.

KEYWORDS:

Cellular therapies; Drug therapies; Large animal models; Primate models; Questionnaire; Translation

PMID:
25902036
DOI:
10.1016/j.expneurol.2015.04.008
[Indexed for MEDLINE]
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