Therapeutic Development in the
Absence of Predictive Animal Models
of Nervous System Disorders
Proceedings of a Workshop
Lisa Bain, Sheena M. Posey Norris, Noam I. Keren, and
Clare Stroud, Rapporteurs
Forum on Neuroscience and
Nervous System Disorders
Board on Health Sciences Policy
Health and Medicine Division
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
THE NATIONAL ACADEMIES PRESS • 500 Fifth Street, NW • Washington, DC 20001
This project was supported by contracts between the National Academy of Sciences and the Alzheimer’s Association; Brain Canada Foundation; Cohen Veterans Bioscience; the Department of Health and Human Services’ Food and Drug Administration (5R13FD005362-02) and National Institutes of Health (NIH) (HHSN26300089 [Under Master Base # DHHS-10002880]) through the National Center for Complementary and Integrative Health, National Eye Institute, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, and NIH Blueprint for Neuroscience Research; Department of Veterans Affairs (VA240-14-C-0057); Eli Lilly and Company; Foundation for the National Institutes of Health; Gatsby Charitable Foundation; Janssen Research & Development, LLC; Lundbeck Research USA; Merck Research Laboratories; The Michael J. Fox Foundation for Parkinson’s Research; National Multiple Sclerosis Society; National Science Foundation (BCS-1064270); One Mind; Pfizer Inc.; Pharmaceutical Product Development, LLC; Sanofi; Society for Neuroscience; and Takeda Development Center Americas, Inc. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for this project.
International Standard Book Number-13: 978-0-309-45513-8
International Standard Book Number-10: 0-309-45513-8
Digital Object Identifier: https://doi.org/10.17226/24672
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Printed in the United States of America
Cover image courtesy of Dr. Thomas Hartung, Johns Hopkins University, Baltimore, Maryland.
Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2017. Therapeutic development in the absence of predictive animal models of nervous system disorders: Proceedings of a workshop. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/24672.
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PLANNING COMMITTEE ON THERAPEUTIC DEVELOPMENT FOR NERVOUS SYSTEM DISORDERS IN THE ABSENCE OF PREDICTIVE ANIMAL MODELS OF DISEASE1
STEVEN HYMAN (Chair), Broad Institute of Massachusetts Institute of Technology and Harvard University
RITA BALICE-GORDON, Sanofi
LINDA BRADY, National Institute of Mental Health
LUCIE BRUIJN, The ALS Association
ROBERT CONLEY, Eli Lilly and Company
NITA FARAHANY, Duke University School of Law
TIFFANY FARCHIONE, Food and Drug Administration
LAWRENCE GOLDSTEIN, University of California, San Diego
JOHN KRYSTAL, Yale School of Medicine
DAVID MICHELSON, Merck Research Laboratories
HOWARD NUSBAUM, National Science Foundation
TODD SHERER, The Michael J. Fox Foundation for Parkinson’s Research
STEVIN ZORN, MindImmune Therapeutics, Inc.
Health and Medicine Division Staff
CLARE STROUD, Forum Director
SHEENA M. POSEY NORRIS, Program Officer
NOAM I. KEREN, Associate Program Officer
DANIEL FLYNN, Senior Program Assistant
ANDREW M. POPE, Director, Board on Health Sciences Policy
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
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FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS1
STEVEN HYMAN (Chair), Broad Institute of Massachusetts Institute of Technology and Harvard University
STORY LANDIS (Vice Chair), Director Emeritus, National Institute of Neurological Disorders and Stroke
SUSAN AMARA, Society for Neuroscience
RITA BALICE-GORDON, Sanofi
KATJA BROSE, Cell Press
EMERY BROWN, Harvard Medical School and Massachusetts Institute of Technology
DANIEL BURCH, Pharmaceutical Product Development, LLC
SARAH CADDICK, Gatsby Charitable Foundation
ROSA CANET-AVILES, Foundation for the National Institutes of Health
MARIA CARRILLO, Alzheimer’s Association
E. ANTONIO CHIOCCA, Harvard Medical School
TIMOTHY COETZEE, National Multiple Sclerosis Society
JONATHAN COHEN, Princeton University
FAY LOMAX COOK, National Science Foundation
BRUCE CUTHBERT, National Institute of Mental Health (until September 2016)
BILLY DUNN, Food and Drug Administration
EMMELINE EDWARDS, National Center for Complementary and Integrative Health (until September 2016)
JOSHUA GORDON, National Institute of Mental Health
HANK GREELY, Stanford University
RAQUEL GUR, University of Pennsylvania
MAGALI HAAS, Cohen Veterans Bioscience
RAMONA HICKS, One Mind
RICHARD HODES, National Institute on Aging
STUART HOFFMAN, Department of Veterans Affairs
MICHAEL IRIZARRY, Eli Lilly and Company
INEZ JABALPURWALA, Brain Canada Foundation
FRANCES JENSEN, University of Pennsylvania
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
GEORGE KOOB, National Institute on Alcohol Abuse and Alcoholism
WALTER KOROSHETZ, National Institute of Neurological Disorders and Stroke
ALAN LESHNER, American Association for the Advancement of Science (Emeritus)
HUSSEINI MANJI, Janssen Research & Development, LLC
DAVID MICHELSON, Merck Research Laboratories
PATRICIO O’DONNELL, Pfizer Inc.
JAMES OLDS, National Science Foundation
ATUL PANDE, Tal Medical
STEVEN PAUL, Voyager Therapeutics, Inc.
RODERIC PETTIGREW, National Institute of Biomedical Imaging and Bioengineering
EMILIANGELO RATTI, Takeda Pharmaceuticals International
TODD SHERER, The Michael J. Fox Foundation for Parkinson’s Research
DAVID SHURTLEFF, National Center for Complementary and Integrative Health
PAUL SIEVING, National Eye Institute
NORA VOLKOW, National Institute on Drug Abuse
STEVIN ZORN, MindImmune Therapeutics, Inc.
Health and Medicine Division Staff
CLARE STROUD, Forum Director
SHEENA M. POSEY NORRIS, Program Officer
NOAM I. KEREN, Associate Program Officer
DANIEL FLYNN, Senior Program Assistant
JIM BANIHASHEMI, Financial Officer
HILARY BRAGG, Program Coordinator
ANDREW M. POPE, Director, Board on Health Sciences Policy
Reviewers
This Proceedings of a Workshop has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published Proceedings of a Workshop as sound as possible and to ensure that the Proceedings of a Workshop meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the process. We wish to thank the following individuals for their review of this Proceedings of a Workshop:
REBECCA DRESSER, Washington University School of Law
KENNETH DUCKWORTH, National Alliance on Mental Illness
FRED H. GAGE, The Salk Institute for Biological Studies
WILLIAM J. MARTIN, BlackThorn Therapeutics, Inc.
LEE L. RUBIN, Harvard University
DAVID WHOLLEY, Foundation for the National Institutes of Health
Although the reviewers listed above have provided many constructive comments and suggestions, they did not see the final draft of the Proceedings of a Workshop before its release. The review of this Proceedings of a Workshop was overseen by ELI Y. ADASHI, Brown University. He was responsible for making certain that an independent examination of this Proceedings of a Workshop was carried out in accordance with institutional procedures and that all review comments were carefully considered.
Responsibility for the final content of this Proceedings of a Workshop rests entirely with the rapporteurs and the institution.
Contents
Organization of the Proceedings
2 Drug Development for Nervous System Disorders: Overview of Challenges and Potential Opportunities
Overview of Potential Opportunities
Translating Discoveries to Treatments
4 New Modeling Approaches for Nervous System Disorders
Genetically Engineered Primate Models
Computational Quantitative Systems Pharmacology Modeling of Brain Circuits
Are Novel Modeling Approaches Changing the Outlook for CNS Drug Discovery?
5 Private-Sector Thresholds for Investment in Neuroscience Clinical Trials
Crossing the Threshold for Investment
Balancing Innovation and Investment at Biotechnology Companies
A Venture Capitalist Perspective
Public−Private Partnerships and Other Precompetitive Consortia
Increasing the Probability of Success for Drug Development
Ensuring Safety in First-in-Human Trials
Conducting Trials in Vulnerable Populations
Including Patient Perspectives and Natural History of Disease in Ethics Discussions
Perspectives from the FDA and European Medicines Agency (EMA)
New Approaches in Establishing Safety and Conducting Toxicology Studies
