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Suggested Citation:"Front Matter." 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: 10.17226/24672.
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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

images

THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu

Suggested Citation:"Front Matter." 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: 10.17226/24672.
×

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

Additional copies of this publication are available for sale from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.

Copyright 2017 by the National Academy of Sciences. All rights reserved.

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.

Suggested Citation:"Front Matter." 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: 10.17226/24672.
×

Image

The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president.

The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. C. D. Mote, Jr., is president.

The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president.

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Learn more about the National Academies of Sciences, Engineering, and Medicine at www.national-academies.org.

Suggested Citation:"Front Matter." 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: 10.17226/24672.
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Image

Reports document the evidence-based consensus of an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and committee deliberations. Reports are peer reviewed and are approved by the National Academies of Sciences, Engineering, and Medicine.

Proceedings chronicle the presentations and discussions at a workshop, symposium, or other convening event. The statements and opinions contained in proceedings are those of the participants and have not been endorsed by other participants, the planning committee, or the National Academies of Sciences, Engineering, and Medicine.

For information about other products and activities of the National Academies, please visit nationalacademies.org/whatwedo.

Suggested Citation:"Front Matter." 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: 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.

Suggested Citation:"Front Matter." 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: 10.17226/24672.
×

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Suggested Citation:"Front Matter." 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: 10.17226/24672.
×

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.

Page viii Cite
Suggested Citation:"Front Matter." 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: 10.17226/24672.
×

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

Suggested Citation:"Front Matter." 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: 10.17226/24672.
×

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.

Suggested Citation:"Front Matter." 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: 10.17226/24672.
×

Responsibility for the final content of this Proceedings of a Workshop rests entirely with the rapporteurs and the institution.

Suggested Citation:"Front Matter." 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: 10.17226/24672.
×
Page R1
Suggested Citation:"Front Matter." 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: 10.17226/24672.
×
Page R2
Suggested Citation:"Front Matter." 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: 10.17226/24672.
×
Page R3
Suggested Citation:"Front Matter." 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: 10.17226/24672.
×
Page R4
Suggested Citation:"Front Matter." 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: 10.17226/24672.
×
Page R5
Suggested Citation:"Front Matter." 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: 10.17226/24672.
×
Page R6
Suggested Citation:"Front Matter." 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: 10.17226/24672.
×
Page R7
Page viii Cite
Suggested Citation:"Front Matter." 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: 10.17226/24672.
×
Page R8
Suggested Citation:"Front Matter." 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: 10.17226/24672.
×
Page R9
Suggested Citation:"Front Matter." 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: 10.17226/24672.
×
Page R10
Suggested Citation:"Front Matter." 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: 10.17226/24672.
×
Page R11
Suggested Citation:"Front Matter." 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: 10.17226/24672.
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Page R12
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Therapeutic Development in the Absence of Predictive Animal Models of Nervous System Disorders: Proceedings of a Workshop Get This Book
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Compared with other disease areas, central nervous system (CNS) disorders have had the highest failure rate for new compounds in advanced clinical trials. Most CNS drugs fail because of efficacy, and the core issue underlying these problems is a poor understanding of disease biology. Concern about the poor productivity in neuroscience drug development has gained intensity over the past decade, amplified by a retraction in investment from the pharmaceutical industry. This retreat by industry has been fueled by the high failure rate of compounds in advanced clinical trials for nervous system disorders.

In response to the de-emphasis of CNS disorders in therapeutic development relative to other disease areas such as cancer, metabolism, and autoimmunity, the National Academies of Sciences, Engineering, and Medicine initiated a series of workshops in 2012 to address the challenges that have slowed drug development for nervous system disorders. Motivated by the notion that advances in genetics and other new technologies are beginning to bring forth new molecular targets and identify new biomarkers, the Academies hosted the third workshop in this series in September 2016. Participants discussed opportunities to accelerate early stages of drug development for nervous system disorders in the absence of animal models that reflect disease and predict efficacy. This publication summarizes the presentations and discussions from the workshop.

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