Cell and Gene Therapies for Neurologic Diseases /

This volume, part of the 'Handbook of Clinical Neurology' series, focuses on the application of cell and gene therapies in the treatment of neurological diseases. Edited by Howard J. Federoff and Roger A. Barker, it compiles the latest research and methodologies in the field, providing ins...

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Bibliographic Details
Main Authors:	Federoff, Howard J. (Author), Barker, Roger A. (Author)
Corporate Author:	ScienceDirect (Online service)
Format:	eBook
Language:	English
Published:	Amsterdam, Netherlands : Elsevier, [2024]
Edition:	First edition.
Series:	Handbook of clinical neurology ; Volume 205.
Subjects:	Nervous system > Diseases. Nervous System Diseases Système nerveux > Maladies. Electronic books.
Online Access:	Connect to the full text of this electronic book

Table of Contents:

Intro
Cell and Gene Therapies for Neurologic Diseases
Copyright
Handbook of Clinical Neurology 3rd Series
Foreword
Preface
Contributors
Contents
Section I: Cellular therapies
Chapter 1: Introduction to stem cell biology and its role in treating neurologic disorders
Introduction to Stem Cells
Stem cells in life and regeneration
Pluripotent stem cells
Cell Replacement Using Pluripotent Stem Cells
Single cell-type cell replacement in the brain
Stem cell-based circuit reconstruction in the brain
Transplant Immunology Applied to Stem Cell Neural Grafts in the Brain
Allogeneic or autologous grafting-Cell intrinsic factors
Allogeneic or autologous grafting-Cell extrinsic factors
New possibilities for mediating graft rejection in the stem cell era
Universal, immune evasive cells
Reprogramming in Regenerative Neuroscience
Direct conversion into induced neurons
In vivo conversion
References
Chapter 2: History of cellular grafting for central nervous system repair-A clinical perspective
Introduction
Preclinical Work in Parkinson Model Triggered the First Clinical Interest
First Clinical Trials With Cellular Grafting: The Rise and Fall of Adrenal Medulla Transplantation in PD
Translation of Human Fetal Dopaminergic Neurons Toward the Clinic
Open-Label Clinical Trials With Human Fetal Dopaminergic Neurons: First Evidence of Surviving and Functional Grafts in P
Major Setback for Cellular Grafting by Sham Surgery-Controlled Clinical Trials With Human Fetal Dopamine Neurons
Other Cell Sources For Dopaminergic Neuron Replacement: No Clinical Success
New Insight Into The Pathogenesis of PD by Human Fetal Dopamine Grafts
Revival of the Field of Cellular Grafting and Clinical Translation of Stem Cells
What Can We Learn From the History of Cellular Grafting?.
Why Have GDNF and NRTN Trials Had Modest Clinical Outcomes?
Future Directions
Acknowledgments
References
Section III: General considerations (for cell and gene therapies)
Chapter 6: Clinical/surgical considerations
Clinical Factors
Precision of diagnosis
Disease heterogeneity
Stage of disease
Consent and capacity
Comorbidity
Other inclusion and exclusion criteria
Pregnancy and conception
Concomitant medications
Acceptability of trial design
Surgical Factors
Advanced product delivery options
Practices to date
Specific instruments
FHC STARDRIVE
Duration of administration-Acceptability
Simultaneous bilateral administration
Documenting effects and adverse effects
Neurosurgical Factors Relevant to Trial Design
References
Chapter 7: Ethics of gene and cell therapy development for neurologic disorders
Introduction
Conclusion and Future Prospects
References
Chapter 8: Clinical trial designs and endpoints
An Introduction into Trial Design
Patient and Public Engagement in Trial Design
Trial Inclusivity and Diversity
Strategies for engaging cultural and ethnic minorities
Using national health service data as a recruitment tool
Determining Sample Size
Defining Study Populations
Participant identification challenges
Randomization, Stratification and Minimization
Control Arms
The placebo effect
Ethical considerations
Types of controls
Clinical Endpoints for Gene and Cell Therapy Trials
Efficacy endpoints
Measures of target engagement and establishing optimal dosing
Safety endpoints
Concluding Remarks
References
Chapter 9: Immunology of cell and gene therapy approaches for neurologic diseases
Introduction
Basic Premise of How the Immune System and the Brain Interact
Critical Factors of the Afferent Arm.
Tissue incompatibility
Pre-exposure status of the recipient of a cellular graft or gene therapy
Repeated treatments
Mitigation steps
Cell Therapy Procedures
Gene therapy
Mitigation steps
Tissue composition, antigen-presenting cells
Vascularization, origin of endothelium
Mitigation steps
Mode of implantation into the brain of cells and vectors
Mitigation steps
Immunization
Mitigation steps
Factors and Properties of the Efferent Arm of the Immune Response
Homing of activated lymphocytes to the site of inflammation
Localized homing
Mitigation steps
Blood-brain barrier properties
Mitigation steps
Immunosuppression
Duration of treatment
Immunosuppressive Regimens in the Ongoing Clinical Trials With Stem Cell-Derived Cell Products for Parkinson's Dis
Detection of Immune Responses or Graft Rejection
Rejection treatment
Summary
References
Chapter 10: Scaling of cell and gene therapies to population
Introduction
Treatment Schemes/Regimes and Their Implications for Manufacturing Concepts and Scales
Pragmatism of Early Clinical Trials in Regenerative Medicine
From Clinical Development to Commercial Phase
Industrializing Cell Manufacturing
References
Chapter 11: The health economics of cell and gene therapies
Introduction
Value-Based Assessment
Cost utility analysis
Economic perspective
Discounting
Highly specialized technology evaluation
Evidence Generation Challenges
Management of uncertainty
Outcomes-based reimbursement
Affordability
Future Directions
References
Section IV: Disease specific interventions using cells and genes
Chapter 12: Disease-specific interventions: The use of cell and gene therapies for Parkinson disease
Introduction
Cell Therapy Approaches For Treating PD.