Abstract
Despite great advances in basic neuroscience knowledge, the improved understanding of brain functioning has not yet led to the introduction of truly novel pharmacological approaches to the treatment of central nervous system (CNS) disorders. This situation has been partly attributed to the difficulty of predicting efficacy in patients based on results from preclinical studies. To address these issues, this review critically discusses the traditional role of animal models in drug discovery, the difficulties encountered, and the reasons why this approach has led to suboptimal utilization of the information animal models provide. The discussion focuses on how animal models can contribute most effectively to translational medicine and drug discovery and the changes needed to increase the probability of achieving clinical benefit. Emphasis is placed on the need to improve the flow of information from the clinical/human domain to the preclinical domain and the benefits of using truly translational measures in both preclinical and clinical testing. Few would dispute the need to move away from the concept of modeling CNS diseases in their entirety using animals. However, the current emphasis on specific dimensions of psychopathology that can be objectively assessed in both clinical populations and animal models has not yet provided concrete examples of successful preclinical–clinical translation in CNS drug discovery. The purpose of this review is to strongly encourage ever more intensive clinical and preclinical interactions to ensure that basic science knowledge gained from improved animal models with good predictive and construct validity readily becomes available to the pharmaceutical industry and clinical researchers to benefit patients as quickly as possible.
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Acknowledgements
We thank the following colleagues (listed in alphabetical order) who provided comments to the Subcommittee on Animal Models of the American College of Neuropsychopharmacology (ACNP) Medication Development Task Force: Dr Anton Bespalov, Dr Floyd E Bloom, Dr Graeme Bilbe, Dr Linda Brady, Dr Jacqueline Crawley, Dr Haim Einat, Dr Irving Gottesman, Dr Todd Gould, Dr Christian Heidbreder, Dr John H Kehne, Dr Peter Kelly, Dr Paul J Kenny, Dr Philip LoGrasso, Dr Husseini K Manji, Dr David Morilak, Dr Paul Patterson, Dr Hans Rollema, Dr Svetlana Semenova, Dr Judith Siuciak, Dr Claes Wahlestedt, Dr Lois Winsky, and three anonymous reviewers. AM was supported by NIH grants U01MH69062, 2R01DA11946, 1R01DA023209, and 1R01DA023926, and Tobacco Related Disease Research Program grant 15RT-0022 from the State of California, USA. MAG was supported by NIH grants 5R01DA02925, 5R01MH071916, and 5R01MH52885, and by the Veterans Affairs VISN 22 Mental Illness Research, Education, and Clinical Center. Finally, the authors wish to thank Dr Svetlana Semenova for assistance with references.
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AM declares that she has received contract research support from Intracellular Therapeutics Inc., and Lundbeck Research USA Inc., and an honorarium from Abbott GmbH and Co. during the past 3 years. CC declares that over the past three years he has received honoraria for consulting from GlaxoSmithKline, Aesculapius Farmaceutici, and Pfizer. MAG declares that over the past 3 years he has received compensation from Abbott, Acadia, Addex, Amgen, AstraZeneca, Epix, Jazz, Organon, Omeros, San Diego Instruments, Serono, and Wyeth-Ayerst. MT and TS declare that, except for income received from their primary employers, no financial support or compensation has been received from any other individual or corporate entity over the past 3 years for research or professional service, and they have no personal financial holdings that could be perceived as constituting a potential conflict of interest.
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Markou, A., Chiamulera, C., Geyer, M. et al. Removing Obstacles in Neuroscience Drug Discovery: The Future Path for Animal Models. Neuropsychopharmacol 34, 74–89 (2009). https://doi.org/10.1038/npp.2008.173
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DOI: https://doi.org/10.1038/npp.2008.173
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