دانلود کتاب Translational Neuroscience : Fundamental Approaches for Neurological Disorders

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Contents Editor Bio Contributors Chapter 1: Introduction Introduction References Part I: Molecular Approaches Chapter 2: Gene Therapy of CNS Disorders Using Recombinant AAV Vectors Introduction Recombinant AAV Vectors Gene Therapy of CNS Disorders Arising from Metabolic Defects Gene Therapy of Movement Disorders Summary References Chapter 3: NGF and BDNF Gene Therapy for Alzheimer’s Disease Introduction Alzheimer’s Disease Background Symptoms and Neuropathology AD Gene Therapy NGF Gene Therapy for Alzheimer’s Disease Discovery and Effects of NGF NGF Gene Therapy: Phase I Ex Vivo Clinical Trial NGF Gene Therapy: Phase 1 and 2 In Vivo Clinical Trials BDNF Gene Therapy for Alzheimer’s Disease Rationale Preclinical Studies of BDNF Gene Therapy Improved Tools for Gene Delivery to the Brain: Real-Time Imaging and Convection Enhanced Delivery of AAV2-BDNF in AD Gene Therapy in AD: Delivery of Other Therapeutic Genes Gene Therapy and Amyloid Degradation RNA Interference in AD Other Gene Therapy in AD Future Gene Therapy for AD Summary References Chapter 4: GDNF and AADC Gene Therapy for Parkinson’s Disease Introduction AAV Delivery to the Putamen Axonal Transport Clinical Experience with AAV2-hAADC for PD Neurotrophin Gene Therapy Conclusion References Chapter 5: GAD Gene Therapy for Parkinson’s Disease Background Preclinical Data Phase I Study Phase II Study Summary References Chapter 6: Antisense Oligonucleotides for Amyotrophic Lateral Sclerosis SOD1 C9ORF72 miRNAs and ALS Pharmacodynamics Biomarkers for ASO in ALS Conclusion References Chapter 7: Gene Therapy for Inborn Errors of Metabolism: Batten Disease Introduction Identifying the Target Disease Developing the Gene Therapy Approach Vectors Delivery to the CNS Strategy for Preclinical Development Strategy for Second Generation Preclinical Development Translation to Clinic: Safety and Toxicology Studies Regulatory Hurdles and Strategies Clinical Strategy Safety Parameters Efficacy Parameters Assembling the Clinical Team Identifying Inclusion/Exclusion Criteria Funding for Clinical Translation Lessons Learned Summary References Chapter 8: Gene Therapy for Spinal Cord Injury Introduction Gene Delivery for Axonal Growth Using Ex Vivo Modified Cells In Vivo Gene Delivery to the Spinal Cord Temporal Regulation of Gene Expression Directional Growth of Axons and Target Innervation Activating the Intrinsic Regenerative Program by Gene Delivery Nonneuronal Targets for SCI Gene Therapy Conclusions References Chapter 9: Gene Therapy for Epilepsy Introduction Modulatory Neuroactive Peptides Neurotrophic Factors Adenosine Ion Channels DREADD Receptors Conclusion References Chapter 10: Translating Gene Therapy for Pain from Animal Studies to the Clinic Introduction Animal Studies of Gene Transfer for Pain DRG Transduction by Skin Inoculation Gene Transfer by Intrathecal or Intraneural Delivery Gene Delivery by Intraparenchymal Injection Translation to Clinical Trial General Considerations Preproenkephalin for Inflammatory Pain Characterization of the Vector Clinical Trials of the Enkephalin-Expressing Vector Clinical Trial of HSV-GAD in Neuropathic Pain Future Directions Concluding Thoughts References Part II: Cellular Approaches Chapter 11: Stem Cells for Parkinson’s Disease Introduction History of Cell Therapy Fetal Nigral Transplants Stem Cell Differentiation of DA Neurons Current Approaches to Stem Cell Therapy Conclusions and Future Directions References Chapter 12: Could Stem Cells Be Used to Treat or Model Alzheimer’s Disease? Introduction AD Neuropathology and the Amyloid Cascade Hypothesis Properties and Sources of Neural Stem Cells Transplantation of Stem Cells for AD Cell Replacement Neurotrophic Mechanisms Delivery of Disease-Modifying Proteins Modulation of Neuroinflammation Unique Challenges to Clinical Translation Stem Cells Self-Renew The Challenges of Scale and Delivery Could Induced Pluripotent Stem Cells Be Used to Treat or Model AD? Transplantation of iPSC-Derived Cells Modeling AD with iPSCs Conclusions References Chapter 13: Stem Cells for Amyotrophic Lateral Sclerosis Introduction Stem Cell Types Autologous Versus Allogenic Transplantation Animal Models Neural Stem Cells Evidence from Animal Studies Clinical Trials of Neural Stem Cells The Future of Neural Stem Cells Mesenchymal Stem Cells Evidence from Animal Studies Differentiation and Survival Clinical Trials of MSCs The Future of MSC Therapy Bone Marrow Stem Cells Evidence from Animal Studies Clinical Trials of Bone Marrow Stem Cells The Future of Bone Marrow Stem Cells Olfactory Ensheathing Cells Evidence from Animal Studies Clinical Trials of Olfactory Ensheathing Cells Umbilical Cord Blood Closing Thoughts References Chapter 14: Stem Cells for Multiple Sclerosis Introduction “Classical” Stem Cell Therapy: Replacing Lost Oligodendrocytes for Myelin Repair (Fig. 14.1) Immune Reconstitution: Hematopoietic Stem Cell Therapy “Restorative” Cell Therapy Remyelination Suppressing Inflammation, Modulating Immunity Neuroprotection Cell Fusion Diffuse Damage Clinical Translation Conclusion References Chapter 15: Cell Therapy for Pediatric Disorders of Glia Cell Types for Cell Replacement Disease Targets for Glial Cell Therapy Approaches to Cell-Based Therapy Neural stem and Progenitor Cell-Based Treatment of Enzymatic Disorders Clinical Considerations in the Use of Cell Transplantation for Developmental Myelin Disorders Conclusion References Chapter 16: Neural Stem Cells for Spinal Cord Injury Introduction Isolation and Characteristics of Neural Stem Cells Neural Stem Cells Directly Isolated from the Developing Spinal Cord Embryonic Stem Cells Driven to Neural Stem Cells Induced Pluripotent Stem Cells Driven to Neural Stem Cells Direct Differentiation of Somatic Cells into Neural Stem Cells In Vivo Studies of Neural Stem Cell Therapy for Spinal Cord Injury Formation of Novel Synaptic Relays Across Sites of Injury Grafts of Human ESC- or iPSC-Derived NSCs to Sites of SCI Mechanistic Studies of Neural Stem Cell-Induced Axonal Growth The Path of Neural Stem Cell Translation to the Clinic Other Neural Stem Cell Approaches for SCI Future Perspectives References Chapter 17: Marrow-Derived Mesenchymal Stromal Cells in the Treatment of Stroke Stroke Is a Major Cause of Human Disability MSC Have Multiple Mechanisms of Action Issues Related to MSC Generation and Transport Preclinical Data Clinical Trials of MSC in Human Subjects with Stroke Principles of Brain Repair and MSC Therapy After Stroke Summary References Chapter 18: Glioma Stem Cells Introduction Cerebellar Neuron and Glia Development Cell of Origin in Glioma Stem Cell Hypotheses Characteristics of a Stem Cell Identification of CSCs CD133 L1CAM and CD133+ Cells CD15 CD44/Id1 Nestin Integrin α6 Musashi-1 EphA2 and EphA3 Embryonic Stem Cell Markers Therapeutic and Prognostic Implications from Stem Cell Markers CSC Radio and Chemotherapy Resistance Possible Treatment Options to Target Glioma Stem Cells Immunotherapy and Stem Cells Gene Therapy and Stem Cells Final Summary References Part III: Novel Pharmacological Approaches Chapter 19: Discovery of Potent Gamma Secretase Modulators for the Treatment of Alzheimer’s Disease References Chapter 20: Blocking the Nogo-A Signaling Pathway to Promote Regeneration and Plasticity After Spinal Cord Injury and Stroke Introduction: Myelin Associated Neurite Growth Inhibitors—Focus on Nogo-A The Central Nervous System Is a Hostile Environment for Axonal Regeneration: History of Discovery The Neurite Growth Inhibitory Protein Nogo-A: Description of Nogo Signaling and Possible Pharmacological Interventions Physiological Functions of Nogo-A Regeneration and Plasticity after CNS Injury and in CNS Disease Stimulation of Regeneration by Upregulating Intrinsic Neuronal Growth Mechanisms Nogo-A Neutralization Improves Regeneration and Promotes Plasticity in Animal Models of Spinal Cord Injury and Stroke Suppression of the Nogo-A Pathway in Animal Models of Spinal Cord Injury Nogo-A Neutralization by Antibodies Blockade of Nogo-A Receptors and Signaling Suppression of Nogo-A Signaling in Animal Models of Stroke Nogo-A Neutralization by Antibodies Suppression of Nogo-A Receptor Activation and Signaling Nogo-A in Amyotrophic Lateral Sclerosis (ALS) Nogo-A in Multiple Sclerosis (MS) Preparing Translation: Preclinical Studies for Nogo-A Blocking Agents Interventions Blocking Nogo-A Signaling in Clinical Trials Spinal Cord Injury Ischemic Stroke Amyotrophic Lateral Sclerosis (ALS) Multiple Sclerosis (MS) Conclusions References Chapter 21: Intrinsic Neuronal Mechanisms in Axon Regeneration After Spinal Cord Injury Introduction Why Exploring the Intrinsic Mechanisms? Loss of Intrinsic Axon Growth Ability in Mammalian CNS Neurons Development-Dependent Mechanisms KLFs cAMP mTOR Injury-Induced Mechanisms “Preconditioning” Effect in Sensory Neurons Strategies that Enhancing the Intrinsic Axon Regenerative Ability “Rejuvenating” Adult CNS Neurons with Transcription Factors Reactivating Trophic Responses with Growth Factors and cAMP Modulating PTEN/mTOR Pathway Modulating SOCS3/STAT Pathway Triggering Axon Regeneration by Inflammation Perspectives References Chapter 22: Voltage-Gated Ion Channels as Molecular Targets for Pain Introduction Sodium Channels as Molecular Targets for Pain “Peripheral” Sodium Channels NaV1.7 NaV1.8 NaV1.9 NaV1.3 Voltage-Gated Calcium Channels N-type Calcium Channels T-type Calcium Channels Voltage-Gated Potassium Channels Horizons and Prospects References Part IV: Activity-Dependent Plasticity and Neurorehabilitation Chapter 23: Rehabilitation-Dependent Neural Plasticity After Spinal Cord Injury Neuronal Control of Normal and Impaired Locomotion Physiological Basis of Human Locomotion Gait Disorder Following Spinal Cord Injury Reflexes and Muscle Tone Biomechanical Muscle Transformations Therapeutic Approaches Recovery of Locomotor Function in Human SCI Neurological and Functional Recovery Therapeutic Approaches Contributors to Recovery Conclusion References Chapter 24: Neural Prostheses for Neurotrauma Introduction Delivery of Electrical Stimulation Properties of Pulse Trains Types of NPs Surface NPs That Enhance Gait Surface NPs That Enhance Upper Limb Function Therapeutic Carry-Over Effects Implanted NPs Implanted NPs That Enhance Gait Epidural and Intraspinal Stimulators Implanted NPs That Enhance Upper Limb Function NPs for Bladder Control NPs for Overactive Bladder NPs That Block Nerve Conduction to Reduce Spastic Hypertonus Concluding Remarks References Chapter 25: Why Is Functional Electrical Stimulation Therapy Capable of Restoring Motor Function Following Severe Injury to the Central Nervous System? Introduction Functional Electrical Stimulation Functional Electrical Stimulation Therapy FES Therapy for Lower Limb in Stroke FES Therapy for Lower Limb in SCI FET for Restoration of Upper Limb Function Following Stroke FES Therapy for Restoration of Upper Limb Function following SCI Our Contributions to FES Therapy Selected Processes in the Healthy Central Nervous System Pertinent to Neurorecovery following an Injury to the Central Nervous System Neuroplasticity and the Healthy Adult Brain The Healthy Neurological System and Exercise The Injured Neurological System, Neurogenesis, and Exercise The Injured Neurological System and Functional Electrical Stimulation Therapy Conclusion References Chapter 26: Deep Brain Stimulation for Neuropsychiatric Disorders Introduction Limbic System Obsessive-Compulsive Disorder Depression Addiction PTSD and Anxiety Anorexia Nervosa Conclusions References Chapter 27: Novel Interventions for Stroke: Nervous System Cooling Introduction Optimized Stroke Modeling Using Conventional Models Optimized Stroke Modeling with the Rodent Filament Model Optimized Stroke Modeling Advantages Therapeutic Hypothermia Conclusions References Chapter 28: Rehabilitation Strategies for Restorative Approaches After Stroke and Neurotrauma Substrates for Rehabilitation Strategies Neurorehabilitation Strategies Strengthening and Aerobic Fitness Exercise Task-Oriented Training Robotic-Assisted Upper Extremity Training Mobility Training Noninvasive Brain Stimulation Other CNS and PNS Stimulation Adjuncts Brain–Machine Interfaces Other Possibly Complementary Interventions Pharmacologic Agents Tele-rehabilitation Combinational Strategies Outcomes Conclusion References Chapter 29: Bridging the Chasm Between Scientific Discovery and a Pivotal Clinical Trial for a CNS Disorder: A Checklist Challenges Common to CNS Disorders Preclinical Validation Prior to Entering Human Study Good Laboratory Practice Reduces Experimental Bias Preclinical Therapeutic Development After Validation of Experimental Efficacy General Requirements for Clinical Trials and the Goals of Various Study Phases Establishing Clinical Trial Guidelines Consideration in Planning a Clinical Trial Program Protocol Concern #1: What Is the Most Appropriate Type of Participant to Enroll in Each Phase of a Trial Program? Protocol Concern #2: What Would Be the Most Accurate, Sensitive, and Reliable Outcome Measure for the Chosen Clinical Target? Protocol Concern #3: How Is a Clinical Endpoint Threshold Selected to Determine Whether the Therapeutic Provides a Meaningful Clinical Benefit to the Experimental Arm in Comparison to an Appropriate Control Group? Conclusions References Chapter 30: Conclusion