Targeted Therapy for the Central Nervous System

Formulation, Clinical Challenges, and Regulatory Strategies

1st Edition - October 7, 2024
Imprint: Academic Press
Editors: Viral Patel, Mithun Singh Rajput, Jigna Samir Shah, Tejal Mehta
Language: English
Paperback ISBN:
9 7 8 - 0 - 4 4 3 - 2 3 8 4 1 - 3
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 2 3 8 4 0 - 6

Targeted Therapy for the Central Nervous System: Formulation, Clinical Challenges, and Regulatory Strategies presents research on various delivery methods of drugs to the central n… Read more

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Targeted Therapy for the Central Nervous System: Formulation, Clinical Challenges, and Regulatory Strategies presents research on various delivery methods of drugs to the central nervous system and brain. This volume examines targeted therapies for neurodegenerative disorders and succinctly outlines the future of drug delivery systems, highlighting significant advancements specifically relating to central nervous system delivery. This book will be of great interest to researchers working in the field of neuroscience and pharmacology as well as clinicians (pharmacists, radiologists, psychiatrists).

Title of Book
Cover image
Title page
Table of Contents
Copyright
Dedication
Contributors
Foreword
Preface
Acknowledgments
Unveiling new frontiers in treating neurological disorders
Chapter 1. Etiology and treatment challenges for neurodegenerative disorders
1 Introduction
2 Etiology of neurodegenerative disorders
2.1 Genetic factors
2.1.1 Alzheimer's disease-related genes
2.1.2 Parkinson's disease
2.1.3 Huntington's disease-related gene
2.1.4 Amyotrophic lateral sclerosis
2.2 Environmental factors
2.2.1 Heavy metals
2.2.2 Pesticides
2.2.3 Air pollutants
2.3 Traumatic brain injuries
2.4 Age-related processes
2.4.1 Oxidative stress (OS)
2.4.2 Mitochondrial dysfunction
2.4.3 Accumulation of cellular damage
2.4.4 Impaired proteostasis
2.4.5 Neuroinflammation
2.4.6 Impaired autophagy and lysosomal dysfunction
2.4.7 Genetic susceptibility and epigenetic changes
2.4.8 Cellular senescence
3 Treatment challenges in neurodegenerative disorders
3.1 Limited understanding of underlying causes
3.2 Lack of biomarkers
3.3 Disease heterogeneity
3.4 Blood-brain barrier
3.5 Symptomatic treatment versus disease modification
3.6 Regulatory hurdles
3.7 High failure rates in clinical trials
4 Strategies to overcome treatment challenges
5 Conclusion
Chapter 2. Etiology and treatment challenges for neurotraumatic and psychiatric disorders
1 Introduction
2 Etiological factors of neurotraumatic-associated psychiatric disorders
2.1 Genetic factors related to susceptibility
2.2 Environmental factors related to causal effect
2.3 Early psychological factors as a predeterminant
3 The interplay of the neuropathological link between neurotrauma and psychiatric disorders
3.1 Neuroinflammatory pathway as the precursor
3.2 Neurotransmitter dysfunction
3.3 Neuroplasticity of maladaptive neurotransmission
4 Current treatment challenges
5 Possible novel therapeutic approaches
6 Conclusion
Chapter 3. Barriers to progress of neurotherapeutics: Getting drugs to the brain
1 Introduction
2 Physiological and pharmacological role of blood brain barrier
2.1 Intercellular junctions
3 Approaches invade through the BBB
3.1 Chemical methods
3.2 Biological methods
3.3 Novel drug delivery systems
3.3.1 Liposomes
3.3.2 Polymeric nanoparticles
3.3.3 Solid–lipid nanoparticles and nanostructured lipid carriers
3.4 Invasive techniques
3.4.1 Intracerebral implants
3.4.2 Intrathecal/interstitial delivery
3.4.3 Biological tissue delivery
3.4.4 Invasive disruption strategies
3.5 Other pathways to CNS
4 Conclusion
Chapter 4. IGF-II conjugated nanocarrier for brain targeting
1 Introduction
1.1 Insulin-like growth factor-II
1.2 Role of IGF-II in physiological function
2 Brief physiology of blood brain barrier
3 Nanocarriers as vehicle for brain delivery
4 Involvement of IGF-II in treating brain diseases
5 Preclinical investigations for therapeutics effects of IGF-II nanocarriers in neurological disorders
5.1 Depression
5.2 Parkinson's disease
5.3 Alzheimer's disease
5.4 Schizophrenia
5.5 Huntington's disease
6 Potential applications and clinical translation
7 Conclusion
Chapter 5. ApoE potential in CNS drugs targeting and as CNS therapeutic
1 Introduction
2 Blood-brain barrier (BBB)
3 Apolipoprotein E (ApoE) and its role in CNS delivery
3.1 Apolipoprotein E: Structure and functions
3.2 ApoE's involvement in neurological disorders (NDs)
3.2.1 Alzheimer's disease (AD)
3.2.2 Cognitive impairment
3.2.3 Traumatic brain injury (TBI)
3.3 Neuroprotective role of ApoE2
3.4 ApoE's as a CNS drug delivery vehicle
4 ApoE-mediated CNS delivery strategies
4.1 Receptor-mediated transcytosis (RMT)
4.2 Lipoprotein nanoparticle formulations using ApoE
4.3 Nanomicelles delivery using ApoE
4.4 Delivery of siRNA to CNS
5 Future directions
6 Conclusions
Chapter 6. Transferrin functionalized nanoparticles for targeted drug delivery in biological systems
1 Introduction
2 Lipid-based NPs
3 Polymeric NPs
4 Inorganic NPs
5 Carbon-based NPs
6 Methodology for conjugation of transferrin
6.1 EDC coupling
6.2 EDC-NHS coupling
6.3 Post-insertion method
6.4 N,N-dicyclohexyl-carbodiimide (DCC) coupling method
6.5 Azide alkyne cycloaddition reaction
6.6 Surface activation method
6.7 Glutaraldehyde cross-link method
7 Applications
7.1 Drug delivery to the brain
7.2 Drug delivery-cancer
7.3 Breast cancer
7.4 Liver cancer
7.5 Melanoma
7.6 Lung cancer
7.7 Multidrug resistance
7.8 Use of nanoparticles for imaging
7.9 Use of nanoparticles in photothermal therapy
8 Conclusion
Chapter 7. Surface engineered multimodal magnetic nanoparticles for neurodegenerative diseases
1 Introduction
1.1 Neurodegenerative diseases (NDDs)
1.2 Blood brain barrier (BBB)
1.3 Targeting approaches to the brain
1.3.1 Active targeting
2 Magnetism and magnetic nanoparticles
3 Magnetic nanoparticles in neurodegenerative diseases management
4 Surface modification
4.1 Introduction
4.1.1 Methods used for surface modification
4.2 Ligands for surface modification
4.2.1 Selective binding
4.2.2 Receptor-mediated delivery
4.2.3 Enhanced drug accumulation
4.2.4 Active targeting
4.3 Types of ligands
4.3.1 Glycoproteins
4.3.2 Vitamin as a ligands
4.3.3 Carbohydrates ligands
4.3.4 Cardiolipins
4.3.5 Peptide
4.3.6 Polyethylene glycol (PEG)
5 Techniques to identify the surface modification
5.1 Transmission electron microscopy
5.2 Nanoparticles tracking analyzer (NTA)
5.3 X-ray diffraction
5.4 Fourier transform infrared spectroscopy
5.5 Nuclear magnetic resonance (NMR) spectroscopy
5.6 Magnetic force microscopy (MFM)
5.7 Thermal Gravimetric Analysis (TGA)
6 Human trials on surface-engineered magnetic nanoparticles
7 Conclusion
List of abbreviation
Chapter 8. Tau targeting biomimetic nanoparticles
1 Introduction
2 Synthesis and disposition of tau protein
3 Folding of tau proteins
4 Distribution of tau protein
5 Metabolism and degradation of tau proteins
6 Tauopathies and their classification
7 Current treatment of tauopathies and challenges in treating tauopathies
7.1 Tauopathies
7.2 Treatment approaches for tauopathies
8 Concept of biomimetic nanoparticles
9 Biomimetics: In treating tauopathies
10 Cell membrane biomimetics
11 Advantages
12 Challenges and future perspectives
Chapter 9. Stem cell therapy as a novel concept to combat CNS disorders
1 Introduction
2 CNS disorders
3 SCs and its type
3.1 MSCs
3.1.1 BM-MSCs
3.1.2 UC-MSCs
3.1.3 AD-MSCs
3.2 ESCs
3.3 Neural stem cells
3.4 Induced pluripotent stem cells (iPSCs)
4 SCs therapy and CNS disorders
4.1 AD
4.1.1 SC therapy and AD
4.2 Traumatic brain injury
4.2.1 TBI and stem cell therapy
4.3 PD
4.3.1 SCs therapy in PD
4.4 ALS
4.4.1 SCs therapy in ALS
4.5 MS
4.5.1 SCs therapy in multiple sclerosis
5 Conclusion
Chapter 10. SR-B1 receptor targeting in CNS disorders
1 Introduction
2 SR-B1-structure, function, and location
2.1 Structure
2.2 Biological distribution
2.3 Physiological functions mediated by SR-B1 receptor
2.3.1 HDL-CE pathway
2.3.2 Reverse cholesterol transport
2.3.3 Steroidogenesis
3 Role of SR-B1 in peripheral pathologies
3.1 Atherosclerosis and CVS-related disorders
3.2 Hepatic metabolic disorders
3.3 Viral infections
3.4 Cancer
4 CNS drug delivery and challenges
5 CNS pathologies associated with SR-B1 receptor
5.1 Alzheimer's disease
5.2 Glioblastoma
5.3 Rett syndrome
5.4 Stroke
6 Molecular signaling cascades associated with SR-B1 receptor
6.1 PI3K/AKT signaling cascade
6.2 Pregnancy-associated plasma protein-A (PAPP-A)
6.3 Inflammasome signaling
6.4 Interferon-α
6.5 p38 MAPK
6.6 Nuclear factor erythroid 2-related factor 2
6.7 Toll-like receptor-2
6.8 TNF-α
7 Summary and conclusion
List of abbreviations
Chapter 11. β- and γ-secretases as therapeutic targets for Alzheimer's disease
1 An overview of Alzheimer's disease etiology
2 Amyloid hypothesis of AD
3 Drug discovery approaches to target amyloid
4 Therapeutic agents targeting BACE-1
4.1 β-secretase: An overview
4.2 Challenges targeting β-secretase
4.3 β-secretase targeting agents
4.4 Acyl guanidine-based inhibitors
4.5 Amidine-, thioamidine- and aminooxazoline xanthene-based inhibitors
4.6 Non-peptidic hydroxyethyl amine (HEA) derived structures
4.7 Iminothiadiazinane dioxide-associated inhibitors
4.8 Amide- and amine-based lead structures
4.9 Other reported lead structure classes
5 Therapeutic agents targeting γ-secretase
5.1 γ-secretase: An overview
5.2 Challenges targeting γ-secretase
5.3 γ-secretase targeting agents
5.4 γ-secretase inhibitors
5.5 γ-secretase modulators
6 Other related targets
7 Conclusion
List of abbreviations
Chapter 12. Minimally invasive nasal depot (MIND) technique for direct BDNF AntagoNAT delivery to the brain
1 CNS disorders
1.1 Stroke
1.2 Epilepsy
1.3 Parkinson's disease
1.4 Alzheimer disease
2 Role of brain derived neurotrophic factor (BDNF) and BDNF-AntagoNAT in CNS disorders
3 Challenges in CNS therapy
3.1 Chemical challenges
3.1.1 Receptor-mediated transcytosis (RMT)
3.1.2 Receptor agonists or antagonists and enzyme modulation
3.2 Transport-mediated challenges
3.3 Structural challenges
3.3.1 Focused ultrasound-enhanced drug delivery
3.3.2 Nanoparticles
3.3.3 Exosomes
3.3.4 Liposomal transport
4 Conventional delivery approaches for CNS diseases like AD and PD
4.1 Intraventricular/intrathecal injections
4.2 Pumps
5 Novel approaches for drug delivery directly to the CNS
5.1 The olfactory pathway (intranasal route)
5.2 Endoscopic skull base surgery technique
5.3 Heterotopic mucosal graft technique
6 Minimally invasive nasal depot (MIND) technique
7 MIND approach for direct BDNF-AntagoNAT delivery to brain
8 Case study one
9 Case study two
10 Conclusion
Chapter 13. Immunosuppressive and immunomodulatory therapies
1 Background
1.1 The immune system and human body
1.2 Relationship between central nervous system and immune responses
2 Immunosuppressive therapies in CNS disorders
2.1 Autoimmune encephalitis
2.2 Neuromyelitis optica
2.3 Multiple sclerosis
2.4 Alzheimer's disease
2.5 Parkinson's disease
2.6 Huntington's disease
2.7 Emerging trends and future implications
3 Immunomodulatory therapies in oncology
3.1 Relationship between tumors and immune responses
3.2 Immune checkpoint inhibitors
3.3 T-cell therapy
3.4 Vaccines for cancer
3.5 Mechanisms of action and clinical applications of immunomodulatory therapies
3.6 Challenges and side effects
4 Personalized medicine and immunotherapy
4.1 Biomarker identification and genetic profiling
4.1.1 CNS diseases
4.1.2 Cancer
4.2 Personalized immunotherapy approaches
4.2.1 Synergistic therapies: Combinations that increase efficacy
5 Future implications of immunotherapy
5.1 Nanotechnology in immunotherapy
5.1.1 Systematic drug delivery based on nanoparticles
5.1.2 Improving immune activation
5.1.3 Immunomodulatory nanomedicines
5.2 Gene editing techniques
5.2.1 CAR-T cell therapies improvement
5.2.2 Creating universal donor cells
5.2.3 Precision immune editing
6 Conclusion
Chapter 14. CRISPR/Cas9 gene editing: A new hope for Alzheimer's disease
1 Introduction
2 CRISPR/Cas9 as a developing gene tool
3 Composition of CRISPR/Cas9
4 CRISPR/Cas9 for treating Alzheimer's disease
4.1 Treating early onset AD
4.2 Treating sporadic AD
5 Functionalities of CRISPR/Cas9 while fabricating gene therapy for Alzheimer's disease
6 Gene delivery pathways
6.1 Viral vectors
6.2 mRNA approach of delivery
6.3 Protein nanocomplex based delivery
7 Future prospects
8 Conclusion
Chapter 15. Artificial intelligence: Ways and means for central nervous system (CNS) delivery
1 Introduction
2 Challenges in delivering therapies to the CNS
3 The significance of effective CNS drug delivery
4 AI in drug discovery and development
4.1 Drug discovery and AI: Current state of the art
4.2 AI-driven target identification and validation
4.3 Predictive modeling for CNS drug candidates
5 AI in personalized medicine
5.1 Personalized medicine and its relevance to CNS disorders
5.2 AI-powered patient classification for CNS therapies
5.3 Customizing CNS treatments through AI-derived insights
6 Drug formulation and delivery technologies
6.1 Nanotechnology and AI: Partners in drug delivery advancements
6.2 AI's guiding hand in developing CNS drug delivery systems
7 Predictive modeling for CNS diseases
7.1 Utilizing machine learning for CNS disease diagnosis and prognosis
7.2 AI's role in predicting drug responses for CNS disorders
7.3 Early detection of neurodegenerative conditions with AI
8 Neuroimaging and AI
8.1 AI-based analysis of neuroimaging data
8.2 Real-time monitoring and AI-driven feedback
8.3 Adaptive drug delivery for CNS disorders
9 Regulatory and ethical considerations
9.1 Navigating regulatory hurdles in AI-powered CNS treatments
9.2 Ethical dilemmas in the realm of AI-enhanced healthcare
9.3 Protecting patient data privacy in the era of AI in CNS healthcare
10 Case studies and applications
10.1 Exemplary outcomes of AI-enhanced CNS drug delivery
10.2 AI advancements in specific CNS disorders
10.3 Challenges encountered and lessons gleaned from real-world deployments
11 Future trends and challenge
12 Conclusion
Chapter 16. Carbon dots as versatile nano-architectures for the treatment of neurological disorders
1 Introduction
2 Synthesis of carbon dots
3 Bioimaging with carbon dots and properties thereof
4 Carbon dots as a therapeutic agent for brain disorders
4.1 Carbon dots for mitigating Parkinson's disease
4.2 Applied therapeutics of carbon dots for treating Alzheimer's disease
4.3 Ability of carbon dots in crossing blood brain barrier
5 Future prospects
6 Conclusion
Chapter 17. Animal models for clinical evaluation
1 Introduction
2 Animal models of Alzheimer's disease
3 Animal models of Parkinson's disease
4 Animal models of Huntington's disease
5 Animal models of epilepsy
6 Animal models of multiple sclerosis
6.1 Subtypes of MS
7 Animal models of traumatic brain injury
7.1 Primary traumatic brain injury
7.2 Primary TBI can be classified into several subtypes
7.3 Secondary traumatic brain injury
7.4 Secondary injuries include
8 Animal models of schizophrenia
9 Animal models of anxiety
9.1 Mechanism and pathophysiology of anxiety
10 Animal models of depression
11 Animal models of attention-deficit hyperkinetic disorder
11.1 Inattention symptoms
11.2 Hyperactivity-impulsivity symptoms
11.3 Neurotransmitter imbalance
11.4 Neural circuitry
11.5 Neurodevelopmental factors
11.6 Neuroinflammation and immune system dysregulation
11.7 Neurocognitive impairments
12 Animal models of migraine
13 Conclusion
Chapter 18. Medical device: Development of next-generation devices from an engineering perspective
1 Introduction
2 Classification of medical device
3 Bio materials used for medical devices
3.1 Metals
3.2 Polymers
3.3 Ceramics and composites
4 Applications of artificial intelligence and machine learning for development of medical devices
4.1 Predictive modeling and simulation
4.2 Optimized design and materials
4.3 Remote monitoring and data analysis
4.4 Personalized treatment and adaptation
4.5 Data analysis and insights
4.6 Enhanced diagnostics and prognostics
4.7 Energy efficiency and power management
4.8 Security and privacy
4.9 Regulatory compliance and risk assessment
4.10 Accelerated R&D and simulation
5 Regulatory approval process for medical devices and challenges ahead
5.1 Postmarket regulation and processes
6 Current status of medical devices
7 Conclusion
Chapter 19. Regulation of nanomaterials and nanomedicines for clinical applications
1 Introduction
2 Properties of nano materials
2.1 Electronic and optical properties
2.2 Magnetic properties
2.3 Mechanical properties
2.4 Thermal properties
2.5 Catalytic properties
3 Clinical applications
3.1 Cancer diagnosis
3.2 Antineoplastics
3.3 Targeted drug delivery
3.4 Cellular imaging
3.5 Biosensors
3.6 Anti-microbial/antibacterial agents
4 Need for regulations and regulatory challenges
4.1 Need for regulations
4.2 Regulatory challenges
5 Current global regulations
5.1 Regulations for nanomedicine as per USFDA44
5.1.1 USFDA guidance
5.1.2 505(b) (2) submission
5.2 Regulatory approval process for nanomedicine in EMA/EU45
5.2.1 Characterization of nanomaterials
5.2.2 Producing cycles
5.2.3 Preclinical studies
5.2.4 Clinical studies
5.2.5 Risk assessment
5.2.6 Analytical methods
5.2.7 Regulatory strategies
6 Conclusion
Chapter 20. Regulatory considerations for the use of biomarkers and personalized medicine in CNS drug development
1 Introduction
2 Approaches in CNS drug development
2.1 New molecule discovery
2.1.1 Target identification and validation
2.1.2 Hit identification
2.1.3 Lead determination
2.1.4 Lead optimization
2.2 Preclinical evaluation of CNS drug
2.2.1 In vitro studies
2.2.2 Acute toxicity studies
2.2.3 Toxicity studies due to dose repetition
2.2.4 Pharmacokinetic studies
2.2.5 Pharmacodynamic studies
2.2.6 Efficacy studies
2.2.7 Safety pharmacology studies
2.2.8 Genotoxicity and carcinogenicity studies
2.3 Clinical testing of CNS drugs
2.4 Regulatory assessment
2.5 Post-approval safety surveillance
3 Imperatives of CNS drug development
4 Evolution of biomarkers and personalized medicine in CNS drug development
4.1 Quality attributes of biomarkers for CNS drug development
4.2 Biomarker qualification and validation techniques
4.3 Biomarker-based target identification
4.4 Integrating biomarkers in preclinical studies and clinical trials
4.5 Concept of personalized medicine in CNS drug development
5 Overview of regulatory considerations on CNS drug development
5.1 Repeat dose toxicity
5.2 Gene toxicity
5.3 Impurities
5.4 Special/hazard studies
5.5 Non-clinical abuse liability
5.6 Dosing in the pediatric population
5.7 Metabolites
5.8 Carcinogenicity
6 Regulatory frameworks on application of biomarkers and personalized medicine in CNS drug development1–118
6.1 US Food and Drug Administration (FDA) guidelines
6.2 World Health Organization (WHO) perspectives on biomarkers and personalized medicine-based CNS drug development
6.3 European medicines agency (EMA) guidelines
6.4 International council for harmonization of technical requirements for registration of pharmaceuticals for human use [ICH] framework
6.5 Pharmaceuticals and Medical Devices Agency (PMDA) guidelines
6.6 Medicines and healthcare products regulatory agency (MHRA) guidelines
7 Benefits and risks of biomarker and personalized medicine utility in CNS drug development
8 Conclusions and future perspectives
Chapter 21. Regulatory toxicology testing for pharmaceuticals
1 Introduction
2 Evolution of toxicology testing
3 Regulatory authorities and guidelines
3.1 Drug regulatory authorities
3.2 Guidelines for toxicology testing
3.2.1 OECD guidelines
3.2.2 ICH guidelines
4 Why are toxicology studies conducted?
5 OECD good laboratory practice (OECD-GLP) in toxicology studies
6 Models in toxicology testing
6.1 In silico models
6.2 In-vitro models
6.3 In-vivo models
7 Alternatives to animal testing
8 Toxicology testing for drug registration
8.1 Toxicity testing requirements at different stages of drug development
8.2 Various toxicity studies
8.2.1 Short term studies
8.2.2 Sub-acute and subchronic toxicity studies
8.2.3 Reproductive and developmental toxicity studies
8.2.4 Carcinogenicity studies
8.3 Special toxicology studies
8.3.1 Phototoxicity study
8.3.2 Immunotoxicity studies
8.3.3 Juvenile toxicity study
8.4 General requirements for toxicology testing
8.4.1 Drug formulation requirements
8.4.2 Bioanalytical methods
8.4.3 Toxicokinetics
9 Regulatory toxicology studies for drug approvals
9.1 505 b1
9.1.1 Concept of first in human dose
9.2 505 b2
9.3 ANDA
10 Impurity qualification
11 Toxicology databases
12 Challenges, advances, and future perspectives
13 Conclusion
Chapter 22. Emerging challenges and opportunities for drug and drug product registrations
1 Introduction
2 Classification of CNS drugs
3 Existing versus new therapy areas for Alzheimer's disease, Parkinson's disease, and multiple sclerosis
4 Personalized therapy options and the change in view point to patient centric development rather than a general mode of development followed so far
5 Lack of precedence and understanding of new drugs and drug delivery modalities for CNS
6 Role of FDA in accelerated regulatory pathways
7 Accelerated approval program for new drugs
8 Adaptive clinical trial designs and challenges
9 Procedure for accelerated assessment in EU
9.1 New drug approval in Europe
9.2 Accelerated regulatory pathways for drug therapies for nervous system disorders in EU
9.3 Clinical trials in EU
9.4 International cooperation
10 Procedure for accelerated assessment for rest of the world
10.1 New drug approval process in China
10.2 Drug approval process in Australia
10.3 New drug applications in India
10.4 Different regulatory pathways and global harmonization
11 Challenges in regulatory approvals for CNS drugs
11.1 Postmarketing surveillance through real-world evidence integration
11.2 Digi health technologies
12 Conclusion
Chapter 23. CRISPR/Cas9 gene editing: A new hope for Parkinson's disease
1 Introduction
2 Existing treatment approaches
2.1 Drugs acting on the dopaminergic system
2.1.1 Levodopa
2.1.2 Dopamine receptor agonist
2.1.3 MAO-B inhibitors
2.1.4 COMT inhibitors
3 Existing genetic therapies for PD
4 What is clustered regularly interspaced short palindromic repeats (CRISPR/Cas 9)
5 Delivery of CRISPR/Cas9 systems
5.1 Viral vectors
5.2 Non-viral vectors
6 The therapeutic use of CRISPR/Cas9 gene editing technology for PD
6.1 LRRK2 gene editing using CRISPR/Cas9
6.2 Deletion of A53T mutation on the SNCA gene
6.3 Deletion of the SNCA gene in synucleinopathy-resistant human dopaminergic neurons
6.4 Using DNA methylation to downregulate SNCA expression
6.5 Conversion of glial cells to dopaminergic neurons
6.6 Restricting the overload of mitochondrial Ca2+
7 Disease modeling using CRISPR/Cas9 in PD
7.1 Cell line models
7.2 Non-primate animal models
7.2.1 Porcine models
7.2.2 Rodent-based models
7.2.3 Zebrafish models
7.3 Non-human primate animal model
8 Challenges/risks of using CRISPR/Cas9 as a gene editing system
9 Conclusions and scope for future work
List of abbreviations
Index

Viral Patel

Dr. Viral Patel currently associated with Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Anand, Gujarat, India as an Assistant Professor. Previously she was serving as Senior Research Associate (Formulation and Development- Research & Development) at Baxter Pharmaceuticals India Private Limited, Ahmedabad, Gujarat, India. Over these years she has gained expertise in the field of pharmaceutical drug product development and technology transfer. She holds a doctorate degree from Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India. She is recipient of prestigious Inspire Fellowship, sponsored by Department of Science and Technology, Govt. of India to pursue her doctoral research. She has many research and review articles published in reputed journals to her credit. She has also written several book chapters published by renowned publishing houses.

Affiliations and expertise

Assistant Professor, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Anand, Gujarat, India

Mithun Singh Rajput

Dr. Mithun Singh Rajput works with the Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India as Assistant Professor. He has expertise in neuropharmacology and received his doctoral degree from the Faculty of Medicine, M.G.M. Medical College, Indore, India. He is a recipient of two years’ National Postdoctoral Fellowship from SERB, Department of Science and Technology, India and is associated with the research project as principal investigator. He has overall teaching and research experience of twelve years. His areas of interest include the diagnosis and mitigation strategies for various neurodegenerative disorders like Alzheimer’s disease and cerebral ischemia, diabetes associated cognitive impairment, etc. He has received five research grants from government agencies and universities. Mithun has two patents, published three book chapters and has edited four books. Mithun is credited with thirty-two publications in peer reviewed indexed journals and currently holds an h-index of eighteen. He has served many government funding agencies, and journals as a reviewer and editorial board member.

Affiliations and expertise

Assistant Professor, Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India

Jigna Samir Shah

Dr. Jigna Shah is currently working as a Professor and Head of the Department of Pharmacology at Institute of Pharmacy, Nirma University, Ahmedabad. She is actively involved in oncology and neurodegenerative disorder research. Currently, she is working as a Principal investigator on one externally funded GSBTM project and two research projects from GSBTM in the area of breast cancer. She has successfully completed five externally funded research projects from GSBTM, AICTE and GUJCOST. Her research has also allowed her to complete a few consultancy assignments in toxicity studies, oncology, neuropharmacology, gastroenterology, and wound healing. She is widely published, having published more than 60 research papers. Shah is active within her research community as a life member of professional organizations such as the Indian Pharmaceutical Association, the Indian Pharmacological Society, the Indian Society for Technical Education and the Indian Society of Pharmacovigilance.

Affiliations and expertise

Professor and Head, Department of Pharmacology at Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India

Tejal Mehta

Dr. Tejal Mehta is currently working as a Professor and Director In-charge at the Institute of Pharmacy, Nirma University, Ahmedabad. She has done her PhD from Sardar Patel University and has over twenty years of teaching and research experience. Her area of research is dissolution enhancement of sparingly soluble drugs and formulation development of conventional and novel drug delivery systems using concepts of QbD-DoE. She has published more than 70 research papers in journals of national and international repute. She has also presented several papers in national and international conferences. She currently also serves as a reviewer of national and international journals in the research area of pharmaceutics and drug delivery. She is an active member of various societies, including the Society of Pharmacovigilance of India.

Affiliations and expertise

Professor and Director In-charge, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India

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Targeted Therapy for the Central Nervous System

Formulation, Clinical Challenges, and Regulatory Strategies

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