Demonstrating efficacy in preclinical studies of cellular therapies for spinal cord injury — How much is enough? Brian K. Kwon a, ⁎, Lesley J.J. Soril b , Mark Bacon c , Michael S. Beattie d , Armin Blesch e , Jacqueline C. Bresnahan d , Mary Bartlett Bunge f , Sarah A. Dunlop g , Michael G. Fehlings h , Adam R. Ferguson i , Caitlin E. Hill j , Soheila Karimi-Abdolrezaee k , Paul Lu l , John W. McDonald m , Hans W. Müller n , Martin Oudega o , Ephron S. Rosenzweig l , Paul J. Reier p , Jerry Silver t , Eva Sykova q , Xiao-Ming Xu r , James D. Guest f , Wolfram Tetzlaff s a ICORD, University of British Columbia, Room 6196, 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada b Rick Hansen Institute, 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada c Spinal Research, Bramley Business Centre, Station Road, Bramley, Guildford, GU5 0AZ, UK d Brain and Spinal Injury Center, Dept. of Neurological Surgery, University of California at San Francisco, 1001 Potrero Ave., Bldg 1, Room 101, San Francisco, CA 94110, USA e Spinal Cord Injury Center, University Hospital Heidelberg, Schlierbacher Landstr. 200A, 69118 Heidelberg, Germany f The Miami Project to Cure Paralysis, 1095 NW 14th Terrace, Miami, FL 33136, USA g The University of Western Australia, Experimental & Regenerative Neurosciences, School of Animal Biology (M317), 35 Stirling Highway, Nedlands 6009, Australia h Division of Neurosurgery and Spinal Program, University of Toronto, Toronto Western Hospital, Suite 4WW-449, 399 Bathurst St., Toronto, Ontario M5T2S8, Canada i Brain and Spinal Injury Center (BASIC), Department of Neurological Surgery, University of California, San Francisco, San Francisco General Hospital, 1001 Potrero Ave, Bldg. 1, Rm 101, San Francisco, CA 94107, USA j Burke Medical Research Institute, Weill Medical College of Cornell University, 785 Mamoroneck Avenue, White Plains, NY 10605, USA k Regenerative Medicine and Spinal Cord Research Center, University of Manitoba, 629-BMSB, 745 Bannatyne Ave, Winnipeg, MB R3E 0J9, Canada l University of California, San Diego, 9500 Gilman Drive, # 0626, La Jolla, CA 92093-0626, USA m International Center for Spinal Cord Injury, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, 716N. Broadway, Baltimore, MD 21205, USA n University of Düsseldorf, Moorenst. 5, 40225 Düsseldorf, Germany o Physical Medicine & Rehabilitation, University of Pittsburgh, W1452 BST, 200 Lothrop Street, Pittsburgh, PA 15213, USA p University of Florida College of Medicine, McKnight Brain Institute, 1149 Newell Dr, Gainesville, FL 32611-0015, USA q Institute of Experimental Medicine AS CR, Videnska 1083, 142 20 Prague 4, Czech Republic r Indiana University School of Medicine, 950W. Walnut Street, Indianapolis, IN 46202, USA s ICORD, University of British Columbia, 818 West 10th Avenue, Vancouver, BC V5Z 1M9, Canada t Case Western Reserve University, Dept. of Neuroscience, School of Medicine, 10900 Euclid Avenue, Cleveland, OH, USA abstract article info Article history: Received 27 April 2013 Accepted 21 May 2013 Available online 29 May 2013 Keywords: Spinal cord injury Cell transplantation therapies Stem cell Clinical trial Preclinical studies Animal model Cellular therapies represent a novel treatment approach for spinal cord injury (SCI), with many different cellular substrates showing promise in preclinical animal models of SCI. Considerable interest therefore exists to trans- late such cellular interventions into human clinical trials. Balanced against the urgency for clinical translation is the desire to establish the robustness of a cellular therapy's efficacy in preclinical studies, thereby optimizing its chances of succeeding in human trials. Uncertainty exists, however, on the extent to which a therapy needs to demonstrate efficacy in the preclinical setting in order to justify the initiation of a lengthy, expensive, and poten- tially risky clinical trial. The purpose of this initiative was to seek perspectives on the level of evidence required in experimental studies of cellular therapies before proceeding with clinical trials of SCI. We conducted a survey of 27 SCI researchers actively involved in either preclinical and/or clinical research of cellular interventions for SCI, and then held a focus group meeting to facilitate more in-depth discussion around a number of translational issues. These included: the use of animal models, the use of injury models and mechanisms, the window for dem- onstrating efficacy, independent replication, defining “relevant, meaningful efficacy” in preclinical studies, and the expectation of therapeutic benefits for cellular interventions. Here we present the key findings from both the survey and focus group meeting in order to summarize and underscore the areas of consensus and Experimental Neurology 248 (2013) 30–44 ⁎ Corresponding author at: Room 6196, Blusson Spinal Cord Centre, Vancouver General Hospital, 818 West 10th Avenue, Vancouver, British Columbia, V5Z 1M9, Canada. Fax: + 1 604 875 5858 E-mail addresses: Brian.Kwon@vch.ca (B.K. Kwon), lsoril@rickhanseninstitute.org (L.J.J. Soril), mark@spinal-research.org (M. Bacon), Michael.beattie@ucsf.edu (M.S. Beattie), armin.blesch@med.uni-heidelberg.de (A. Blesch), Jacqueline.bresnahan@ucsf.edu (J.C. Bresnahan), MBunge@med.miami.edu (M.B. Bunge), sarah.dunlop@uwa.edu.au (S.A. Dunlop), Michael.fehlings@uhn.ca (M.G. Fehlings), Adam.ferguson@ucsf.edu (A.R. Ferguson), Cah2024@med.cornell.edu (C.E. Hill), karimis@cc.umanitoba.ca (S. Karimi-Abdolrezaee), plu@ucsd.edu (P. Lu), mcdonaldj@kennedykrieger.org (J.W. McDonald), Hanswerner.mueller@uni-duesseldorf.de (H.W. Müller), moudega@pitt.edu (M. Oudega), ephronr@gmail.com (E.S. Rosenzweig), reier@ufl.edu (P.J. Reier), sykova@biomed.cas.cz (E. Sykova), Xu26@iupui.edu (X.-M. Xu), jguest@med.miami.edu (J.D. Guest), tetzlaff@icord.org (W. Tetzlaff). 0014-4886/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.expneurol.2013.05.012 Contents lists available at SciVerse ScienceDirect Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr