Molecular and Cellular Therapies for Motor Neuron Diseases - 1st Edition - ISBN: 9780128022573, 9780128025246

Molecular and Cellular Therapies for Motor Neuron Diseases

1st Edition

Editors: Nicholas Boulis Deirdre O’Connor Anthony Donsante
eBook ISBN: 9780128025246
Hardcover ISBN: 9780128022573
Imprint: Academic Press
Published Date: 16th January 2017
Page Count: 336
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Molecular and Cellular Therapies for Motor Neuron Diseases discusses the basics of the diseases, also covering advances in research and clinical trials. The book provides a resource for students that will help them learn the basics in a detailed manner that is required for scientists and clinicians.

Users will find a comprehensive overview of the background of Amyotrophic Lateral Sclerosis (ALS/Lou Gehrig’s Disease) and Spinal Muscular Atrophy (SMA), along with the current understanding of their genetics and mechanisms. In addition, the book details gene and cell therapies that have been developed and their translation to clinical trials.

Key Features

  • Provides an overview of gene and cell therapies for amyotrophic lateral sclerosis (ALS) and other motor neuron diseases
  • Edited by a leading Neurosurgeon and two research scientists to promote synthesis between basic neuroscience and clinical relevance
  • Presents a great resource for researchers and practitioners in neuroscience, neurology, and gene and cell therapy


Advanced graduate students, researchers, and clinicians in the fields of neuroscience, neurology, and gene and cell therapy

Table of Contents

  • List of Contributors
  • Acknowledgment
  • Chapter 1. Molecular and Extracellular Cues in Motor Neuron Specification and Differentiation
    • Abstract
    • Introduction
    • Specification of Neuroectoderm
    • Spinal Cord Patterning
    • The Motor Neuron Progenitor Domain and Initial Neurogenesis
    • Molecular Programs in Newborn Motor Neurons
    • Migration
    • Motor Neuron Subtypes and Targets
    • Extracellular Matrix and the Nervous System
    • Motor Neuron Cell Death
    • The Glial Switch
    • Generating Motor Neurons From Pluripotent Stem Cells
    • Generating Oligodendrocyte Precursor Cells From Pluripotent Stem Cells
    • Conclusion
    • References
  • Chapter 2. Natural History of Amyotrophic Lateral Sclerosis
    • Abstract
    • History
    • Epidemiology
    • Clinical Presentation
    • Pathogenesis
    • Treatments
    • Summary
    • References
  • Chapter 3. Genetics of Amyotrophic Lateral Sclerosis
    • Abstract
    • Introduction
    • Amyotrophic Lateral Sclerosis Genes
    • Protein Aggregation: Superoxide Dismutase 1
    • Dysfunction of mRNA Metabolism: TAR DNA-Binding Protein and Fused in Sarcoma
    • Dysfunction of mRNA and Protein Homeostasis: C9orf72
    • Beyond C9orf72: Dysfunction of Protein Degradation Systems and the Amyotrophic Lateral Sclerosis–Frontotemporal Dementia Associated Genes
    • Disruption of Cytoskeleton: PFN1 and TUBA4A
    • Future Perspectives and Conclusions
    • References
  • Chapter 4. Molecular Mechanisms of Amyotrophic Lateral Sclerosis
    • Abstract
    • Introduction
    • RNA Metabolism
    • Altered RNA Splicing, Transport, and Translation
    • Adenosine Deaminase Acting on RNA 2
    • MicroRNAs
    • Protein Aggregation and Toxicity
    • Superoxide Dismutase 1
    • TAR DNA-binding protein-43
    • Fused in Sarcoma
    • Other Aggregating Proteins
    • C9ORF72
    • Axonopathy and Axonal Transport Defects
    • Cellular Stress
    • Stress Granules
    • Autophagy and Proteasomal Stress
    • Endoplasmic Reticulum Stress
    • Inflammation and Glial Function
    • Astrocytes
    • Microglia
    • Oligodendrocytes
    • T cells
    • Perineuronal Nets and Extracellular Matrix Dysfunction
    • Conclusions
    • References
  • Chapter 5. An Introduction to the Natural History, Genetic Mapping, and Clinical Spectrum of Spinal Muscular Atrophy
    • Abstract
    • Introduction: Epidemiology
    • Historical Context of Spinal Muscular Atrophy: Review of Case Studies and History of Categorization
    • Our Modern Understanding of the Disease: Mapping Efforts and Identification of the Survival Motor Neuron Gene
    • Treatment and Standard of Care
    • Conclusion
    • References
  • Chapter 6. Genetics of Spinal Muscular Atrophy
    • Abstract
    • Introduction
    • The Spinal Muscular Atrophy Gene Region
    • Genetics of 5q Spinal Muscular Atrophy and Phenotype Modification in Man
    • The Biochemical Function of Survival Motor Neuron
    • Spinal Muscular Atrophy Models and Genetic Suppression
    • Development of Therapies Based on the Genetics of Spinal Muscular Atrophy
    • Summary and Future Directions
    • References
  • Chapter 7. Introduction to Gene and Stem-Cell Therapy
    • Abstract
    • Introduction
    • Gene Therapy
    • Stem Cells
    • Routes of Delivery
    • Conclusion
    • References
  • Chapter 8. Gene Therapy for Amyotrophic Lateral Sclerosis: Therapeutic Transgenes
    • Abstract
    • Introduction
    • Antiapoptosis
    • Glutamate Signaling (Glutamate Transporter 1, ADAR2/AMPA)
    • Antioxidant Genes
    • Neurotrophic Factors
    • Tetanus Toxin heavy Chain C-Fragment
    • Angiogenin
    • Single-Chain Antibodies
    • Possible Future Candidates
    • Timing of Therapy
    • Concluding Remarks
    • References
  • Chapter 9. Stem Cell Therapy for Amyotrophic Lateral Sclerosis
    • Abstract
    • Introduction
    • Stem Cells in Amyotrophic Lateral Sclerosis: Microenvironment Modulation
    • Embryonic Stem Cells
    • Bone Marrow-Derived Mesenchymal Stem Cells
    • Peripheral Blood Stem Cells
    • Umbilical Cord Blood Stem Cells
    • Olfactory Ensheathing Cells
    • Neural Progenitor Cells
    • The Future of Stem Cells in Amyotrophic Lateral Sclerosis
    • Conclusions
    • Acknowledgments
    • References
  • Chapter 10. Gene Therapy for Spinal Muscular Atrophy
    • Abstract
    • Introduction
    • Animal Models
    • Strategies of Gene Therapy in Spinal Muscular Atrophy
    • Clinical Trials
    • Closing Remarks
    • Acknowledgments
    • References
  • Chapter 11. Cellular Therapy for Spinal Muscular Atrophy: Pearls and Pitfalls
    • Abstract
    • Introduction
    • Potential Therapeutic Effects of Stem Cells on Spinal Muscular Atrophy Disease Mechanisms
    • The Selection of Cell Types to be Transplanted
    • Embryonic Stem Cell Derived Motor Neuron Precursors for Spinal Muscular Atrophy
    • Induced Pluripotent Stem Cell Derived Motor Neurons as a Cell Source for Transplantation
    • Neural Stem Cells
    • Transplantation of Specific Neural Stem Cell Subpopulations
    • Glial Cells
    • Muscle Cells
    • Minimally Invasive Strategies of Administration to Ease the Clinical Translation: The Cerebrospinal Fluid and Systemic Routes
    • From Benchtop to Clinical Translation: Issues to Overcome
    • Stem Cells for Drug Discovery
    • Conclusions
    • References
  • Chapter 12. Clinical Trials to Date
    • Abstract
    • Situation and Introduction
    • Stem Cell Clinical Trials in Amyotrophic Lateral Sclerosis
    • Europe
    • Asia
    • Conclusions
    • References
  • Index


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About the Editor

Nicholas Boulis

Dr. Nicholas Boulis is a physician scientist whose research interests include biological neurorestoration and neuromodulation through the use of cell, protein and gene delivery to the nervous system. Dr. Boulis graduated Summa Cum Laude from Yale University with distinction in intensive Biology and Philosophy majors and graduated Magna Cum Laude from Harvard Medical School, winning the Harold Lamport Biomedical Research Award.

Dr. Boulis developed a clinical program focusing on peripheral nerve regeneration, spasticity, pain and Parkinson's Disease, applying advanced microsurgical, radiosurgical and ablative and neural augmentation approaches. He has independently organized and secured funding for an outreach/teaching mission to provide surgical therapy to patients in Guatemala requiring treatment for hydrocephalus and spina bifida. To date, "Project Shunt" has provided over 250 free operations to impoverished Guatemalan children.

Affiliations and Expertise

Department of Neurosurgery, Emory University, Atlanta, GA, USA

Deirdre O’Connor

Dr. Deirdre O’Connor is a research scientist who has conducted both basic and translational research throughout her scientific career, from undergraduate through to post-doctoral work. She graduated from the National University of Ireland, Galway with a B.Sc. in Biotechnology and a Ph.D. in Developmental Biology. Her research interests have evolved as into a focus on regenerative medicine and gene therapy with a translational application. She is, currently, on developing gene therapies for Amyotrophic Lateral Sclerosis (ALS) and optimizing delivery methods to the CNS. This work is being undertaken with a view to progressing it through the translational pathway and on to clinical trials.

Affiliations and Expertise

Department of Neurosurgery, Emory University, Atlanta, GA, USA

Anthony Donsante

Dr. Anthony Donsante is a scientist whose research focuses on the development of gene therapies for neurodegenerative diseases. He graduated Magna Cum Laude from Case Western Reserve University with Bachelor of Science degrees in Mathematics and Biology and minors in Artificial Intelligence and History. He went on to earn his Doctorate in Molecular Genetics from Washington University in St. Louis, studying gene therapy for lysosomal storage diseases in the laboratory of Dr. Mark Sands. Dr. Donsante then moved on to a postdoctoral position at the National Institutes of Health, where he developed the first gene therapy for Menkes disease in the laboratory of Dr. Stephen Kaler. Dr. Donsante is currently a Research Associate at Emory University, working with Dr. Nicholas Boulis to develop gene therapies to treat amyotrophic lateral sclerosis.

Affiliations and Expertise

Department of Neurosurgery, Emory University, Atlanta, GA, USA

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