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Translational Neuroscience Translational Neuroscience Mark H. Tuszynski Editor Translational Neuroscience Fundamental Approaches for Neurological Disorders Editor Mark H. Tuszynski Translational Neuroscience Institute University of California-San Diego Veterans Administration Medical Center La Jolla, CA, USA ISBN 978-1-4899-7652-9 ISBN 978-1-4899-7654-3 (eBook) DOI 10.1007/978-1-4899-7654-3 Library of Congress Control Number: 2015944984 Springer New York Heidelberg Dordrecht London © Springer Science+Business Media New York 2016 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Springer Science+Business Media LLC New York is part of Springer Science+Business Media ( www.springer.com ) Contents 1 Introduction . 1 Mark H. Tuszynski Part I Molecular Approaches 2 Gene Therapy of CNS Disorders Using Recombinant AAV Vectors . 9 Giridhar Murlidharan , R. Jude Samulski , and Aravind Asokan 3 NGF and BDNF Gene Therapy for Alzheimer’s Disease . 33 Mark H. Tuszynski and Alan H. Nagahara 4 GDNF and AADC Gene Therapy for Parkinson’s Disease . 65 Krystof Bankiewicz , Waldy San Sebastian , Lluis Samaranch , and John Forsayeth 5 GAD Gene Therapy for Parkinson’s Disease . 89 Michael G. Kaplitt and Matthew J. During 6 Antisense Oligonucleotides for Amyotrophic Lateral Sclerosis . 99 Wade K. Self and Timothy M. Miller 7 Gene Therapy for Inborn Errors of Metabolism: Batten Disease . 111 Dolan Sondhi , Ronald G. Crystal , and Stephen M. Kaminsky 8 Gene Therapy for Spinal Cord Injury . 131 Ioana Goganau and Armin Blesch 9 Gene Therapy for Epilepsy . 155 Thomas J. McCown 10 Translating Gene Therapy for Pain from Animal Studies to the Clinic . 167 Darren Wolfe , David Krisky , James Goss , James Wechuck , Marina Mata , and David J. Fink v vi Contents Part II Cellular Approaches 11 Stem Cells for Parkinson’s Disease . 187 Andrés M. Bratt-Leal and Jeanne F. Loring 12 Could Stem Cells Be Used to Treat or Model Alzheimer’s Disease? . 203 Edsel M. Abud and Mathew Blurton-Jones 13 Stem Cells for Amyotrophic Lateral Sclerosis . 227 Anthony Donsante , Lindsey Nicole Urquia , and Nicholas M. Boulis 14 Stem Cells for Multiple Sclerosis . 259 Pamela Sarkar and Neil Scolding 15 Cell Therapy for Pediatric Disorders of Glia . 275 M. Joana Osorio and Steven A. Goldman 16 Neural Stem Cells for Spinal Cord Injury . 297 Paul Lu , Ruhel Ahmad , and Mark H. Tuszynski 17 Marrow-Derived Mesenchymal Stromal Cells in the Treatment of Stroke . 317 Steven C. Cramer 18 Glioma Stem Cells . 335 Regina Teresa Martuscello , Brent A. Reynolds , and Santosh Kesari Part III Novel Pharmacological Approaches 19 Discovery of Potent Gamma Secretase Modulators for the Treatment of Alzheimer’s Disease . 359 Kevin D. Rynearson , Rudolph E. Tanzi , and Steven L. Wagner 20 Blocking the Nogo-A Signaling Pathway to Promote Regeneration and Plasticity After Spinal Cord Injury and Stroke . 369 Anna Magdalena Guzik-Kornacka , Flóra Vajda , and Martin E. Schwab 21 Intrinsic Neuronal Mechanisms in Axon Regeneration After Spinal Cord Injury . 399 Fengfeng Bei and Zhigang He 22 Voltage-Gated Ion Channels as Molecular Targets for Pain . 415 Gerald W. Zamponi , Chongyang Han , and Stephen G. Waxman Part IV Activity-Dependent Plasticity and Neurorehabilitation 23 Rehabilitation-Dependent Neural Plasticity After Spinal Cord Injury . 439 Lea Awai , Volker Dietz , and Armin Curt Contents vii 24 Neural Prostheses for Neurotrauma . 457 Arthur Prochazka 25 Why Is Functional Electrical Stimulation Therapy Capable of Restoring Motor Function Following Severe Injury to the Central Nervous System? . 479 Mary K. Nagai , Cesar Marquez-Chin , and Milos R. Popovic 26 Deep Brain Stimulation for Neuropsychiatric Disorders . 499 Ausaf A. Bari , Nicolas Kon Kam King , Nir Lipsman , and Andres M. Lozano 27 Novel Interventions for Stroke: Nervous System Cooling . 517 Patrick D. Lyden , Jessica Lamb , and Padmesh S. Rajput 28 Rehabilitation Strategies for Restorative Approaches After Stroke and Neurotrauma . 539 Bruce H. Dobkin 29 Bridging the Chasm Between Scientific Discovery and a Pivotal Clinical Trial for a CNS Disorder: A Checklist . 555 John D. Steeves 30 Conclusion . 581 Mark H. Tuszynski Editor Bio Mark H. Tuszynski , MD, PhD , is a professor of neurosciences and founding director of the Translational Neuroscience Institute at the University of California— San Diego, and a neurologist at the Veterans Administration Medical Center in La Jolla, California. He received his undergraduate and MD degrees from the University of Minnesota in Minneapolis, completed neurology residency at Cornell University Medical Center/The New York Hospital, and subsequently received a PhD in neu- roscience from the University of California—San Diego. Dr. Tuszynski studies basic and translational aspects of neurodegenerative disorders and neurotrauma and the biological basis of learning and memory. ix Contributors Edsel M. Abud , BSc Department of Neurobiology and Behavior , University of California, Irvine , CA , USA Ruhel Ahmad , PhD Department of Neuroscience , University of California at San Diego , San Diego , CA , USA Aravind Asokan , PhD Departments of Genetics, Biochemistry and Biophysics , Gene Therapy Center , University of North Carolina at Chapel Hill, Chapel Hill , NC , USA Lea Awai , PhD Spinal Cord Injury Center , Balgrist University Hospital , Zurich , Switzerland Krystof Bankiewicz , MD, PhD Department of Neurological Surgery , University of California, San Francisco , San Francisco , CA , USA Ausaf A. Bari , MD, PhD Division of Neurosurgery , Toronto Western Hospital , Toronto , ON , Canada Fengfeng Bei , PhD Department of Neurology , F. M. Kirby Neurobiology Center, Boston Children’s Hospital , Boston , MA , USA Harvard Medical School , Boston , MA , USA Nicholas M. Boulis , MD Department of Neurosurgery , Emory University School of Medicine , Atlanta , GA , USA Steven C. Cramer , MD, MMSc Department of Neurology, Anatomy and Neurobiology, and Physical Medicine and Rehabilitation, Sue and Bill Gross Stem Cell Research Center, UC Irvine Institute for Clinical and Translational Science, University of California , Irvine , Irvine, CA , USA Armin Blesch , PhD Spinal Cord Injury Center , Heidelberg University Hospital , Heidelberg , Germany xi xii Contributors Mathew Blurton-Jones , PhD Department of Neurobiology and Behavior , University of California, Irvine , Irvine , CA , USA Andrés M. Bratt-Leal , PhD Parkinson’s Association of San Diego , San Diego , CA , USA Grégoire Courtine , PhD International Paraplegic Foundation Chair in Spinal Cord Repair, Swiss Federal Institute of Technology (EPFL) , Center for Neuroprosthetics, and Brain Mind Institute , Lausanne , Vaud , Switzerland Ronald G. Crystal , MD Genetic Medicine , Weill Cornell Medical College , New York , NY , USA Armin Curt , MD Spinal Cord Injury Center , Balgrist University Hospital , Zurich , Switzerland Volker Dietz , FRCP Spinal Cord Injury Center , Balgrist University Hospital , Zürich , Switzerland Bruce H. Dobkin , MD Ronald Reagan UCLA Medical Center , Los Angeles , CA , USA Department of Neurology , Geffen School of Medicine at the University of California Los Angeles , Los Angeles , CA , USA Reed Neurologic Research Center , Los Angeles , CA , USA Anthony Donsante , PhD Department of Neurosurgery , Emory University Hospital , Atlanta , GA , USA Matthew J. During , MD, DSc Ovid Therapeutics , New York , NY , USA David J. Fink , MD Department of Neurology , University of Michigan , Ann Arbor , MI , USA John Forsayeth , PhD Department of Neurological Surgery , University of California, San Francisco , San Francisco , CA , USA Ioana Goganau , MD Spinal Cord Injury Center , Heidelberg University Hospital , Heidelberg , Germany Steven A. Goldman , MD, PhD Center for Basic and Translational Neuroscience , University of Copenhagen Faculty of Health and Medical Sciences , Copenhagen , Denmark Department of Neurology, Center for Translational Neuromedicine, URMC-Strong Memorial Hospital , University of Rochester Medical Center , Rochester , NY , USA James Goss , PhD PeriphaGen, Inc. , Pittsburgh , PA , USA Anna Magdalena Guzik-Kornacka , PhD Department of Health Science and Technology and Brain Research Institute , ETH Zurich and University of Zurich , Zurich , Switzerland Contributors xiii Chongyang Han , PhD Department of Neurology , Yale University School of Medicine , New Haven , CT , USA Center for Neuroscience and Regeneration Research , Veterans Affairs Medical Center , West Haven , CT , USA Zhigang He , PhD
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