The Role of Animal Models in Evaluating Reasonable Safety and Efficacy for Human Trials of Cell-Based Interventions for Neurologic Conditions

Author:

Regenberg Alan1,Mathews Debra JH1,Blass David M23,Bok Hilary1,Coyle Joseph T4,Duggan Patrick1,Faden Ruth1,Finkel Julia1,Gearhart John D5,Hillis Argye6,Hoke Ahmet6,Johnson Richard7,Johnston Michael8,Kahn Jeffrey9,Kerr Douglas10,King Patricia11,Kurtzberg Joanne12,Liao S Matthew113,McDonald John W14,McKhann Guy15,Nelson Karin B16,Rao Mahendra16,Siegel Andrew W1,Smith Kirby17,Solter Davor18,Song Hongjun5,Sugarman Jeremy1,Vescovi Angelo19,Young Wise20,Greely Henry T21,Traystman Richard J22

Affiliation:

1. Johns Hopkins Berman Institute of Bioethics, Johns Hopkins University, Baltimore, Maryland, USA

2. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland, USA

3. Abarbanel Mental Health Center, Bat Yam, Israel, affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

4. Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts, USA

5. Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA

6. Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA

7. Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, Maryland, USA

8. Division of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland, USA

9. Center for Bioethics, University of Minnesota, Minneapolis, Minnesota, USA

10. Johns Hopkins Transverse Myelopathy Center, Johns Hopkins University, Baltimore, Maryland, USA

11. Georgetown University Law School, Georgetown University, Washington, District of Columbia, USA

12. Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, North Carolina, USA

13. Faculty of Philosophy, Oxford University, Oxford, UK

14. International Center for Spinal Cord Injury, Kennedy Krieger Institute, Baltimore, Maryland, USA

15. Zanvyl/Krieger Mind Brain Institute, Johns Hopkins University, Baltimore, Maryland, USA

16. National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

17. Invitrogen Corporation, Carlsbad, California, USA

18. Institute of Medical Biology, A* STAR, National University of Singapore, Singapore

19. Department of Biological Sciences and Biotechnology, University of Milan, Milan, Italy

20. WM Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey, USA

21. Stanford Law School, Stanford University, Stanford, California, USA

22. University of Colorado at Denver, Denver, Colorado, USA

Abstract

Progress in regenerative medicine seems likely to produce new treatments for neurologic conditions that use human cells as therapeutic agents; at least one trial for such an intervention is already under way. The development of cell-based interventions for neurologic conditions (CBI-NCs) will likely include preclinical studies using animals as models for humans with conditions of interest. This paper explores predictive validity challenges and the proper role for animal models in developing CBI-NCs. In spite of limitations, animal models are and will remain an essential tool for gathering data in advance of first-in-human clinical trials. The goal of this paper is to provide a realistic lens for viewing the role of animal models in the context of CBI-NCs and to provide recommendations for moving forward through this challenging terrain.

Publisher

SAGE Publications

Subject

Cardiology and Cardiovascular Medicine,Neurology (clinical),Neurology

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