The mouse as a model for neuropsychiatric drug development

James R Howe 6th; Mark F Bear; Peyman Golshani; Eric Klann; Stuart A Lipton; Lennart Mucke; Mustafa Sahin; Alcino J Silva

doi:10.1016/j.cub.2018.07.046

The mouse as a model for neuropsychiatric drug development

Curr Biol. 2018 Sep 10;28(17):R909-R914. doi: 10.1016/j.cub.2018.07.046.

Authors

James R Howe 6th¹, Mark F Bear², Peyman Golshani³, Eric Klann⁴, Stuart A Lipton⁵, Lennart Mucke⁶, Mustafa Sahin⁷, Alcino J Silva⁸

Affiliations

¹ Departments of Neurobiology, Psychiatry & Biobehavioral Sciences and Psychology, Integrative Center for Learning and Memory, Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Current address: Neurosciences Graduate Program, Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
² Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³ Departments of Neurology, Psychiatry and Biobehavioral Sciences, Integrative Center for Learning and Memory, Brain Research Institute, University of California, Los Angeles, CA 90095, USA.
⁴ Center for Neural Science, New York University, New York, NY 10003, USA.
⁵ Neuroscience Translational Center and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, CA 92037, and Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA.
⁶ Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
⁷ F.M. Kirby Neurobiology Center, Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁸ Departments of Neurobiology, Psychiatry & Biobehavioral Sciences and Psychology, Integrative Center for Learning and Memory, Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: silvaa@mednet.ucla.edu.

Abstract

Much has been written about the validity of mice as a preclinical model for brain disorders. Critics cite numerous examples of apparently effective treatments in mouse models that failed in human clinical trials, raising the possibility that the two species' neurobiological differences could explain the high translational failure rate in psychiatry and neurology (neuropsychiatry). However, every stage of translation is plagued by complex problems unrelated to neurobiological conservation. Therefore, although these case studies are intriguing, they cannot alone determine whether these differences observed account for translation failures. Our analysis of the literature indicates that most neuropsychiatric treatments used in humans are at least partially effective in mouse models, suggesting that neurobiological differences are unlikely to be the main cause of neuropsychiatric translation failures.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Disease Models, Animal*
Drug Development / statistics & numerical data*
Humans
Mental Disorders / drug therapy*
Mice
Neuropsychiatry

Abstract

Publication types

MeSH terms

Grants and funding