Enabling Novel Treatments for
Nervous System Disorders by
Improving Methods for Traversing the
Blood–Brain Barrier
PROCEEDINGS OF A WORKSHOP
Lisa Bain, 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
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This activity 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; George and Anne Ryan Institute for Neuroscience at The University of Rhode Island; 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: 978-0-309-47307-1
International Standard Book Number-10: 0-309-47307-1
Digital Object Identifier: https://doi.org/10.17226/25044
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Copyright 2018 by the National Academy of Sciences. All rights reserved.
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Cover image courtesy of Dr. Viviana Gradinaru, California Institute of Technology, Pasadena, California.
Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2018. Enabling novel treatments for nervous system disorders by improving methods for traversing the blood–brain barrier: Proceedings of a workshop. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/25044
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PLANNING COMMITTEE ON ENABLING NOVEL TREATMENTS FOR NERVOUS SYSTEM DISORDERS BY IMPROVING METHODS FOR TRAVERSING THE BLOOD–BRAIN BARRIER1
HUSSEINI MANJI (Co-Chair), Janssen Research & Development, LLC
DANICA STANIMIROVIC (Co-Chair), National Research Council of Canada
FRANCESCA BOSETTI, National Institute of Neurological Disorders and Stroke
E. ANTONIO CHIOCCA, Harvard Medical School
VIVIANA GRADINARU, California Institute of Technology
CHENGHUA GU, Harvard Medical School
JAMES KOENIG, National Institute of Neurological Disorders and Stroke
SARAH H. LISANBY, National Institute of Mental Health
ROGER LITTLE, National Institute on Drug Abuse
WILLIAM PARDRIDGE, University of California, Los Angeles
STEVEN PAUL, Voyager Therapeutics, Inc.
ERIC SCHAEFFER, Janssen Research & Development, LLC
AJAY VERMA, United Neuroscience
Health and Medicine Division Staff
CLARE STROUD, Forum Director
SHEENA M. POSEY NORRIS, Program Officer
NOAM I. KEREN, Associate Program Officer
DANIEL FLYNN, Research Assistant
ANDREW M. POPE, Director, Board on Health Sciences Policy
___________________
1The 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, Chan Zuckerberg Initiative
EMERY BROWN, Harvard Medical School and Massachusetts Institute of Technology
JOSEPH BUXBAUM, Icahn School of Medicine at Mount Sinai
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
JAMES DESHLER, National Science Foundation
BILLY DUNN, Food and Drug Administration
MICHAEL EGAN, Merck Research Laboratories
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
GEORGE KOOB, National Institute on Alcohol Abuse and Alcoholism
___________________
1The 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.
WALTER KOROSHETZ, National Institute of Neurological Disorders and Stroke
JOHN KRYSTAL, Yale University
ALAN LESHNER, American Association for the Advancement of Science (Emeritus)
HUSSEINI MANJI, Janssen Research & Development, LLC
DAVID MICHELSON, Merck Research Laboratories (until December 2017)
JAMES OLDS, National Science Foundation (until December 2017)
ATUL PANDE, Tal Medical
STEVEN PAUL, Voyager Therapeutics, Inc.
STEPHEN PEROUTKA, Pharmaceutical Product Development, LLC
RODERIC PETTIGREW, National Institute of Biomedical Imaging and Bioengineering (until November 2017)
EMILIANGELO RATTI, Takeda Pharmaceuticals International
TAREK SAMAD, Pfizer Inc.
DOUGLAS SHEELEY, National Institute of Dental and Craniofacial Research
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
ANDREW WELCHMAN, Wellcome Trust
DOUG WILLIAMSON, Lundbeck
STEVIN ZORN, MindImmune Therapeutics, Inc.
Health and Medicine Staff
CLARE STROUD, Forum Director
SHEENA M. POSEY NORRIS, Program Officer
NOAM I. KEREN, Associate Program Officer
DANIEL FLYNN, Research Assistant
JIM BANIHASHEMI, Financial Officer (until October 2017)
BARDIA MASSOUDKHAN, Financial Associate (from October 2017)
ANDREW M. POPE, Director, Board on Health Sciences Policy
Reviewers
This Proceedings of a Workshop was 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 National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.
We thank the following individuals for their review of this proceedings:
CHOI-FONG CHO, Brigham and Women’s Hospital
AGNES V. KLEIN, Health Canada
ELISA E. KONOFAGOU, Columbia University
SARAH H. LISANBY, National Institute of Mental Health
BERND STOWASSER, Sanofi
AJAY VERMA, United Neuroscience, Inc.
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by LESLIE Z. BENET, University of California, San Francisco. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all
review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.
Contents
Organization of the Proceedings
2 Traversing the Blood–Brain Barrier: Challenges and Opportunities
How the BBB Presents Challenges for Drug Delivery
Overview of Potential Opportunities
3 Modalities and Technologies for Brain Delivery
4 Regulatory Considerations for Drugs That Traverse the Blood–Brain Barrier
5 Accelerating Research and Clinical Translation: Consortia and Public–Private Partnerships