Neuroprotection - Drugs, Markets and Companies

Neuroprotection - Drugs, Markets and Companies published by Jain Pharmabiotech in January, 2012. This report price starts from US $ 5000.

Introduction

Abstract

Summary

This report describes the role of neuroprotection in acute disorders such as stroke and injuries of the nervous system as well as in chronic diseases such as neurodegenerative disorders because many of the underlying mechanisms of damage to neural tissues are similar in all these conditions and several products are used in more than one disorder. Over 500 products have been investigated for neuroprotective effects including those from the categories of free radical scavengers, anti-excitotoxic agents, apoptosis (programmed cell death) inhibitors, anti-inflammatory agents, neurotrophic factors, metal ion chelators, ion channel modulators and gene therapy. Some of the agents are old established pharmaceuticals whereas others are new biotechnology products.

Pathomechanisms of diseases are described with steps at which neuroprotective therapies are directed. Diseases covered include cerebrovascular disorders, traumatic brain injury, spinal cord injury, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy and ischemic optic neuropathy as well as retinal degeneration. Although anesthetics such as propofol are neuroprotective as well, neuroprotection during surgery and anesthesia is discussed with the aim of preventing and treating complications that result in CNS damage.

The report contains a profile of 130 companies that have a neuroprotective product or products along with 110 collaborations. Some of the products in development at academic institutions that do not have a commercial sponsor are also included. Although an up-to-date search of the literature was performed and selected 850 references are included, a considerable amount of information has not been published anywhere else. Clinical trials of various neuroprotective agents are described and failures of trials are analyzed with suggestions for improving the selection of drugs and design of trials.The report is supplemented with 65 tables and 11 figures.

Market analysis of currently used productsthat have a neuroprotective effect are analyzed for the year 2010. Some of these products are approved for other indications but are known to have a neuroprotective effect. With the approval of new products and takeover of markets for obsolete symptomatic therapies, the neuroprotection market value will rise by the year 2015 when it will constitute a major and important component of the CNS market. Forecasts are made until 2020. By that time neuroprotection will be an established part of the neurological practice and measures will be available to achieve this effectively.

Table of Contents

0. Executive Summary

1. Introduction

• Definitions
• Historical development of neuroprotection
• Intrinsic neuroprotective factors
• Neuroprotective gene expression
• Upregulation of GADD34
• Induction of NR4A proteins by CREB in neurons
• Neurotrophic factors
• Intrinsic nonenzymatic antioxidants
• Activation of transcription factor Nrf2
• Intrinsic neuroprotective proteins
• αB-crystallin
• Excitatory amino acid transporters
• Extracellular serine protease thrombin
• Galanin
• Neuroglobin
• Nuclear factor I-A
• Prion protein
• Rai adaptor protein
• Stem cell factor
• Role of the immune system in neuroprotection
• Induction of DNA repair enzymes for neuroprotection
• Pathomechanisms of CNS injury as basis for neuroprotection
• Biomarkers of neurological disorders and neuroprotection
• CNS biomarker identification using proteomics
• Brain imaging for detection of biomarkers
• Role of neuroprotection in various neurological disorders
• Neuroprotection and neuroregeneration
• Acute versus chronic neuroprotection
• Discovery and evaluation of neuroprotective agents
• Neuroprotective drug discovery
• Discovery of CNS drugs that penetrate the blood-brain barrier
• In vitro assays for the evaluation of neuroprotective agents
• Oxidative injury model to test neuroprotective drugs
• Apoptosis model for designing neuroprotective drugs
• Transgenic mouse models of neurological disorders
• Evaluating effects of neuroprotective drugs on living brain slices
• Role of brain imaging in neuroprotective drug discovery and development
• Positron emission tomography
• Role of single photon emission computed tomography
• Functional CT scanning to evaluate cerebrovascular protection
• Magnetic resonance imaging for the evaluation of neuroprotectives
• Application of nanotechnology to neuroprotection
• Evaluation criteria for potential neuroprotective agents

2. Neuroprotective Agents

• Classification of neuroprotective agents
• Activated protein C
• Activity-dependent neuroprotective protein
• Adenosine analogs
• Propentofylline
• Antidepressants
• Antidepressant-induced neurogenesis
• Neurogenesis induced by electroconvulsive therapy
• Neuroprotective effect of selective serotonin reuptake inhibitors
• Antiepileptic drugs as neuroprotectives
• Phenytoin
• Valproic acid
• Levetiracetam
• Antiinflammatory agents
• Aspirin
• Interleukin-1 antagonists
• COX-2 inhibitors
• Nimesulide
• Gold microparticles as anti-neuroinflammatory agents
• Minocycline
• Anti-apoptosis agents
• Activated protein C
• Calpain inhibitors
• Caspase inhibitors
• DNA binding drugs
• Lithium
• Olesoxime
• Omega-3 fatty acids
• Docosahexaenoic acid
• Poly(ADP-ribose) polymerase inhibitors
• Prevention of apoptosis by binding of proNGF to sortilin
• Antioxidants/free radical scavengers
• Free radical generation
• Natural defenses against oxidative stress
• Effects of oxidative damage
• Oxidative damage and aging
• Neuronal damage by free radicals
• Oxidative damage and neurodegenerative disorders
• Measures to control oxidative stress
• Categories of therapeutic antioxidants
• Alpha-phenyl-tert-butylnitrone
• Coenzyme Q10
• Dihydroergocryptine
• Flavonoids
• Mitochondria-targeted antioxidants
• Nanoparticles as neuroprotective antioxidants
• Neuroleptics as antioxidants
• Nitrones
• Translation of antioxidant neuroprotection from preclinical to clinical
• Carbon monoxide and heme oxygenase
• Cell transplants
• Cells secreting neuroprotective substances
• Stem cells
• Stem cell activation for neuroprotection/regeneration by glucocorticoids
• Cytokines
• Erythropoietin
• Non-erythropoietic EPO variants and mimics
• Granulocyte colony-stimulating factor
• Delta-opioid receptor agonists
• FK960
• Gene therapy
• Glucagon-like peptide
• Glatiramer acetate
• Glutamate antagonists
• Neuroprotection by scavenging blood glutamate
• N-acylethanolamines for protection against glutamatergic excitotoxicity
• Glutamate transporters
• Glutamate transporter-mediated neuroprotective effect of drugs
• Neuroprotection by targeting KAI subunit of kainate receptor
• Glycine-proline-glutamate analogs
• Herbal preparations
• Flavonoid wogonin
• Ginseng
• Hydrogen sulfide
• NMDA receptor ion channel complex
• NMDA receptor antagonists
• NMDA NR2B subunit receptor antagonists
• Ifenprodil
• Memantine as a neuroprotective agent
• Magnesium
• NAALADase inhibitors
• Gacyclidine
• N-alkylglycines
• AMPA receptor modulators
• Metabotropic glutamate receptor modulators
• Cannabinoids
• Dexanabinol
• Glutathione
• Heat shock proteins
• Hormones
• Estrogen and neuroprotection
• Neuroprotective effect of estrogen receptor ligands
• Selective estrogen receptor modulators
• Mitochondrial mechanisms of estrogen neuroprotection
• Insulin
• Ion Channel modulators
• Calcium channel blockers
• Ziconotide
• Na+ channel blockers
• Neuroprotective potassium channel inhibitors
• Kynurenine inhibitors
• Leukocyte adhesion inhibitors
• Modafinil
• Neural regeneration protein
• Neurite outgrowth-promoting prostaglandin compounds
• Neuroimmunophilins
• Cyclosporin-A
• FK506
• Rapamycin
• Neurotrophic factors
• Activity-dependent neurotrophic factor
• Bone morphogenetic proteins
• Brain-derived neurotrophic factor
• Ciliary neurotrophic factor
• Fibroblast growth factors
• Glial cell line-derived neurotrophic factor
• Insulin-like growth factor
• Nerve growth factor
• Neurotrophins
• Osteogenic protein-1
• Pigment epithelium-derived factor
• Transforming growth factor-β
• Vascular endothelial growth factor
• Neurotrophic factor-related neuroprotective agents
• Amitriptyline as a TrkA and TrkB receptor agonist
• Colivelin
• Gambogic amide
• Inosine
• Meteorin
• Oxygen-regulated protein 150 kD
• Prosaptide
• Siagoside
• Small molecule activators of the Trk receptors
• Nicotine and nicotinic receptor agonists
• Neuroprotective effect of galantamine mediated via α7nAChRs
• Galantamine-induced Aβ clearance via α7nAChRs
• Nitric oxide-based neuroprotection
• Nitric oxide synthase inhibitors
• Nitric oxide mimetics
• Nootropics
• Piracetam
• Nutraceuticals and food constituents
• Coffee
• Creatine
• Curcumin/curry
• Curcumin as a neuroprotectant in Alzheimer disease
• Curcumin as a neuroprotectant in stroke
• Curcumin as a neuroprotectant in multiple sclerosis
• Mechanism of neuroprotective effect of curcumin
• Glyceryltriacetate
• Green tea
• Nicotinamide
• Resveratrol
• Osmotic diuretics
• Mannitol
• Osteopontin
• Oxygen therapeutics
• Oxygen carriers
• Hemoglobin-based oxygen carriers
• Perfluorocarbons as oxygen carriers
• Hyperbaric oxygen therapy
• Peptides
• C3-derived peptide for neuroprotection and neuroregeneration
• Corticotropin-releasing hormone
• Thyrotropin-releasing hormone
• Vasoactive intestinal peptide
• Pharmacological preconditioning
• PPARs as drug targets for neuroprotection
• Riluzole
• Role of RNA interference in neuroprotection
• Sigma receptor agonists as neuroprotective agents
• SIRT group of proteins
• Statins
• Steroids
• Dehydroepiandrosterone
• HF0220
• Sulforaphane
• Tauroursodeoxycholic acid
• Tetanus toxin as a neuroprotective agent
• Thrombolytic agents as neuroprotective agents
• Uncoupling protein 2
• Vaccines as neuroprotectives
• Vitamins as neuroprotective agents
• Vitamin B12
• Vitamin D
• Non-pharmacological approaches to neuroprotection
• Environmental enrichment
• Mental training
• Physical exercise
• Hypothermia
• Limitations of hypothermia
• Hypothermic neuroprotection in hypoxia-ischemia
• Hibernation induced by hydrogen sulfide
• Ketogenic diet
• Nonpharmacological preconditioning for neuroprotection
• Transcranial magnetic stimulation
• Electrical fields for improvement of cerebral function in neurodegeneration
• Neuroprotective effect of exercise
• Hibernation and neuroprotection
• Suspended animation and neuroprotection

3. Neuroprotection in Cerebrovascular Disease

• Introduction
• Pathophysiology of cerebral ischemia
• Calcium overload
• Ion channel dysfunction in stroke
• Role of oxygen free radicals in cerebral ischemia
• Role of nitric oxide in cerebral ischemia
• Glutamate as a biomarker of stroke
• Cerebral edema in stroke
• Gene expression in response to cerebral ischemia
• Induction of heat shock proteins in stroke
• Role of cytokines and adhesion molecules in stroke
• Tumor necrosis factor-α
• Interleukin-1 and IL-6
• Adhesion molecules
• DNA damage and repair in cerebral ischemia
• Role of neurotrophic factors in stroke
• Problems requiring investigation of the role of NTFs in stroke
• Role of Poly(ADP-ribose) polymerase (PARP) gene
• Role of protease-activated receptor 1
• Reperfusion injury after cerebral ischemia
• Neuroprotection according to zones in cerebral infarction
• Zone of ischemic infarction
• Penumbra
• Current management of stroke
• Neuroprotection in stenosis of intracranial arteries
• Neuroprotection in transient ischemic attacks
• Neuroprotective therapies for stroke
• αB-crystallin as a neuroprotectant in stroke
• Acid-sensing ion channel blockers
• AMPA receptor antagonists as neuroprotectives for stroke
• Zonampanel
• Antiapoptotic neuroprotectives
• NIM811
• Creatine as neuroprotective in stroke
• Lithium as a neuroprotective in stroke
• TUDCA as a neuroprotective in stroke
• Coagulation inhibitors as neuroprotectives
• Heparin and enoxaparin
• Warfarin vs dabigatran
• Apixaban
• Antiepileptic drugs as neuroprotectives in stroke
• Tiagabine
• Topiramate
• Zonisamide
• Anti-HMGB1 monoclonal antibody
• Antioxidant approaches
• Carnosine as a neuroprotective in stroke
• Dehydroascorbic acid
• Tocotrienols
• Uric acid
• Antiglutamate compounds
• MRZ 2/576
• L-Phenylalanine
• Arimoclomol for stroke
• Cardiac glycosides as neuroprotectives in stroke
• Clenbuterol
• Cox-2 inhibitors for ischemic stroke
• Docosahexaenoic acid for ischemic stroke
• Estrogen for stroke
• Extendin-4
• Flavones for neuroprotection in stroke
• Granulocyte-macrophage colony-stimulating factor for cerebral ischemia
• Modulation of histamine H2-receptors
• Inosine for stroke
• Insulin-like growth factor-I
• Intravenous immunoglobulin as neuroprotective in stroke
• Ischemic preconditioning for neuroprotection in stroke
• Ketone bodies for neuroprotection in stroke
• Mineralocorticoid receptor blockade for neuroprotection
• Multifunctional neuroprotective agents
• Nasal delivery of neuroprotective agents in stroke
• Neuroserpin as a neuroprotective in stroke
• N-2-mercaptopropionyl glycine
• NeuroAid
• Neurotrophic factors as neuroprotectives for stroke
• AX200
• Brain-derived neurotrophic factor
• Fibroblast growth factor
• Glial cell line-derived neurotrophic factor
• Insulin-like growth factor-1
• Neuregulin-1
• NO-based strategies for neuroprotection in cerebral ischemia
• Perlecan domain V
• Peroxisome proliferator-activated receptor-γagonists
• PGE2 EP2 receptor activation
• Pioglitazone for reduction of stroke risk in diabetes
• Progesterone
• Proteosome inhibitors
• Statins for prevention and neuroprotection in stroke
• Sildenafil
• Src receptor blockade
• Stroke vaccine
• SUN N4057
• Thrombosis inhibitors
• Aspirin
• Clopidogrel
• Dipyridamole
• Vitamin E for neuroprotection in stroke
• Neuroprotection in reperfusion injury
• Prevention of hemorrhage following ischemic stroke
• Non-pharmacological neuroprotective therapies for stroke
• Preconditioning for neuroprotection against cerebral ischemia
• Hypothermia for neuroprotection in acute stroke
• Hyperbaric oxygen therapy for neuroprotection in acute stroke
• Infrared laser therapy for ischemic stroke
• Neurostimulation of sphenopalatine ganglion
• Neurosurgical procedures for neuroprotection in stroke
• Neurorehabilitation in relation to neuroprotection in stroke
• Cell therapy for stroke
• Stem cell transplant for stroke
• Immortalized cell grafts for stroke
• Stimulation of instrinsic stem cells for repair of brain in stroke
• Neuroprotective vaccines for stroke
• Gene therapy for neuroprotection in cerebrovascular disease
• Regulation of microRNAs for neuroprotection in cerebral ischemia
• RNAi-based therapy for neuroprotection in stroke
• Neuroprotective therapies for cerebral ischemia: clinical trials
• Albumin
• Free radical scavengers
• DP-b99
• Minocycline for neuroprotection in stroke
• Perindopril
• Failed clinical trials of neuroprotection in stroke
• Ancrod
• Aptiganel
• Cerovive
• Citicoline
• Desmoteplase
• Erythropoietin as a neuroprotective in stroke
• SPD 502
• Tirilazad mesylate
• Selfotel
• Lubeluzole
• Nalmefene
• Gavestinel
• Nimodipine
• Sipatrigine
• Causes of failure of stroke trials
• Measures for prevention of failures in stroke trials
• Design of acute stroke trial to facilitate drug approval
• The ideal neuroprotective agent for stroke
• Future prospects for neuroprotection in stroke

4. Neuroprotection in Traumatic Brain Injury

• Introduction
• Cerebral hypoxia/ischemia as a complication of trauma
• Epidemiology of TBI
• TBI in the military
• Pathophysiology of TBI
• Immediate damage following TBI
• Cerebral edema following TBI
• Delayed damage following TBI
• Mechanism of axonal damage after TBI
• Role of neuroinflammation in TBI
• Molecular events following TBI
• BBB damage after TBI
• Chronic traumatic encephalopathy
• Neurocognitive sequelae of TBI
• Changes in neurotrophic factors following TBI
• Changes in neurotransmitters following TBI
• Proteomics of TBI
• Genetic influences on outcome following TBI
• Management of TBI
• Control of intracranial pressure and cerebral edema
• Corticosteroids
• Neuroprotection in TBI
• Antiepileptic drugs for prevention of seizures and neuroprotection
• Antioxidants
• Barbiturates
• β- and γ-secretase inhibitors
• Beta blockers
• Bradykinin B2 antagonists
• Cell cycle inhibitors for TBI
• COX-2 inhibitors for neuroprotection in TBI
• Cyclosporin for neuroprotection in TBI
• Dexanabinol for TBI
• Erythropoietin for neuroprotection in TBI
• Gold implants for neuroprotection in focal TBI
• KN 38-7271
• Levosimendan
• Magnesium sulfate
• Minocycline for TBI
• Nutritional approaches to neuroprotection in TBI
• Branched chain amino acids to ameliorate cognitive impairment in TBI
• Creatine for neuroprotection in TBI
• Nicotinamide for neuroprotection in TBI
• Omega 3 fatty acids as neuroprotectives in TBI
• Neurotrophic factors for TBI
• Neurosteroids as neuroprotective agents for TBI
• NMDA receptor antagonists
• NP-1
• Nogo-A inhibitor
• Oxygen carriers for TBI
• Polyethylene glycol for neuroprotection in TBI
• Propofol for neuroprotection in TBI
• Rapamycin as neuroprotective in TBI
• Simvastatin as neuroprotective in TBI
• Thyrotropin-releasing hormone analogs
• Traxoprodil
• Biological approaches to neuroprotection in TBI
• Antisense approaches to TBI
• Cell therapy for TBI
• Gene therapy for TBI
• Vaccines for TBI
• Non-pharmaceutical approaches to neuroprotection in TBI
• Hyperbaric oxygen therapy for TBI
• Hypothermia
• Reduction of microglial migration after TBI
• Deep brain stimulation for TBI
• Prophylactic neuroprotection against TBI
• Role of helmets in protection against TBI
• Role of physical exercise in protection against TBI
• Clinical trials of neuroprotective agents in TBI
• Ongoing clinical trials in TBI
• Failed clinical trials in TBI
• Differences between clinical trials and studies in animal models of TBI
• Subgroup analysis
• Improving the clinical trial design
• Clinical trials combining multiple treatment strategies
• Shortening the trial time
• Conclusions and future prospects of neuroprotection in TBI

5. Neuroprotection in Spinal Cord Injury

• Introduction
• Pathophysiology of SCI
• Secondary mechanisms of SCI
• Neurotrophic factor changes in SCI
• Management of SCI
• Pharmacological neuroprotective agents for SCI
• 4-aminopyridine
• Antibodies as neurite growth inhibitors in SCI
• Bacterial enzyme chondroitinase ABC
• Docosahexaenoic acid as neuroprotective in SCI
• Erythropoietin as a neuroprotective in SCI
• Free radical scavengers for neuroprotection in SCI
• Gacyclidine
• GYKI 52466
• Immunosuppressants as neuroprotectants in SCI
• Interleukin-10 for neuroprotection in SCI
• Matrix metalloproteinase inhibitors for SCI
• Methylprednisolone
• Minocycline as neuroprotective in SCI
• Neurotrophic factors for neuroprotection after SCI
• Promotion of regeneration of neurons in SCI
• Rho pathway and Rho antagonists in SCI
• Selenium as a neuroprotective for SCI
• Sialidase for enhancing recovery after SCI
• Targeting the inflammatory response for neuroprotection in SCI
• Uric acid as neuroprotective in SCI
• Non-pharmacological approaches to SCI
• Hyperbaric oxygen therapy
• Hypothermia for SCI
• Cell therapy for SCI
• Autoimmune T cells against CNS myelin-associated peptide
• Fetal neural grafts for SCI
• Olfactory-ensheathing cells for SCI
• Oligodendrocyte precursor cells for treatment of SCI
• Schwann cell transplants for SCI
• Transplantation of glial cells for SCI
• Stem cells for SCI
• Bone marrow stem cells for SCI
• Embryonic stem cells for SCI
• Transplantation of induced pluripotent stem cells in SCI
• Transplantation of MSCs for SCI
• Transplantation of NSCs for SCI
• Transdifferentiation of stem cells into cholinergic neurons for SCI
• Gene therapy for SCI
• Combined approaches to spinal cord injury
• Discovery of new targets for neuroprotective therapies in SCI
• Clinical trials in SCI

6. Neuroprotection in Neurodegenerative Disorders

• Introduction
• Pathomechanism of neurodegeneration
• Dual role of aα synuclein in neuroprotection and neurodegeneration
• Lack of neurotrophic factors
• Neuroinflammation in neurodegenerative disorders
• Neurodegeneration associated with protein misfolding
• Modulation of neurodegeneration by molecular chaperones
• Intrabodies targeting protein misfolding in neurodegeneration
• Targeting proteins aggregation to prevent amyloid formation
• Tau and neurodegeneration
• TDP-43 proteinopathy and neurodegenerative diseases
• Role of apoptosis in neurodegenerative disorders
• Role of glia in neurodegeneration
• Role of metals in neurodegeneration
• Viral infections and neurodegeneration
• AIDS and the nervous system
• Avian influenza as cause of neurodegeneration
• Genetic disorders with neurodegeneration
• Batten disease
• Friedrich ataxia
• Pathomechanism of FA
• Neuroprotection in FA
• Niemann-Pick type C disease
• Creutzfeldt-Jakob disease
• Approaches to neuroprotection in neurodegenerative disorders
• Glutamate-based therapies for neurodegenerative disorders
• Mitochondria permeability transition pore complex and neuroprotection

7. Neuroprotection in Parkinson Disease

• Introduction
• Epidemiology of Parkinson's disease
• Pathophysiology of Parkinson's disease
• Oxidative stress
• Excitotoxicity
• Asynchronous neuronal activity
• Apoptosis
• Role of neurotrophic factors
• Role of misfolding proteins
• Genetic factors in PD
• Alteration of dopamine homeostasis
• Neuroprotective strategies for PD based on pathomechanism
• RNAi screening to identify neuroprotective genes in a PD model
• Management of Parkinson's disease
• Limitation of conventionally administered dopamine therapy
• Treatment of dementia associated with PD
• Neuroprotective therapy in PD
• Neuroprotective effect of currently used drugs for PD
• Pramipexole
• Rasagiline mesylate
• Ropinirole
• Selegiline
• Non-pharmacological strategies for neuroprotection in PD
• Effect of exercise and environmental enrichment on PD
• Low-calorie diet in PD
• Development of neuroprotective therapies for PD
• 9-methyl-β-carboline
• Adenosine AA2 receptor antagonists
• Antiapoptotic strategies for PD
• Calcium channel blockers for PD
• Cell therapies for PD
• Stem cells for PD
• Activation of endogenous stem cells and neural precursors
• Cogane
• Creatine and minocycline
• Conserved dopamine neurotrophic factor for PD
• Free radical scavengers for neuroprotection in Parkinson's disease
• Antioxidants
• Melatonin
• Tea extracts as neuroprotectives
• Nicotine as a neuroprotective in PD
• Gene therapy for PD
• Implantation of genetically engineered cells
• Gene therapy using GDNF and neurturin
• Glutamic acid decarboxylase gene therapy
• Parkin gene therapy
• Concluding remarks about gene therapy for PD
• Heat shock protein 70
• Neuroprotective effect of leucine-rich repeat kinase-2 inhibitors
• Neuroprotective effect of DJ-1 protein
• Neurotrophic factors
• GDNF for PD
• Neurturin for PD
• BDNF for PD
• Basic fibroblast growth factor for PD
• Platelet derived growth factor
• Clinical trials with NTFs
• Nrf2-mediated neuroprotection in PD
• Omega-3 polyunsaturated fatty acids
• RAB3B overexpression
• RNAi therapy for PD
• Safinamide
• Sirtuin 2 inhibitors for neuroprotection in PD
• Statins and PD
• Targeting Bax
• Vitamin D for neuroprotection in PD
• Vaccine for PD
• Clinical trials of neuroprotection in Parkinson's disease
• Evaluation of neuroprotective therapies for PD
• Current status and future challenges for neuroprotection in PD

8. Neuroprotection in Alzheimer Disease

• Introduction
• Pathomechanism of Alzheimer's disease
• Role of glutamate transport dysfunction in AD
• Role of neurotrophic factors in the pathomechanism of AD
• Management of Alzheimer's disease
• Neuroprotection in Alzheimer's disease
• Inhibition of Aβ formation and aggregation
• AN-1792
• Cadmium telluride nanoparticles prevent Aβ fibril formation
• Clioquinol
• Colostrinin
• FKBP52 for neuroprotection from Cu toxicity in AD
• Monoclonal antibody m266
• Phenserine
• Secretase inhibitors
• Inhibition of neuroinflammation
• Etanercept
• Neurotrophic factors/ gene therapy
• NGF gene therapy
• AL-108
• Targeting plasminogen activator inhibitor type-1 gene
• Estrogen and AD
• Antioxidants
• NSAIDS
• Memantine
• Dimebon
• Cerebrolysin
• Ginko biloba
• Tetrahydrocannabinol for neuroprotection in AD
• Ladostigil tartrate
• Phosphodiesterase inhibitors as neuroprotectives
• PPAR-γ agonists
• Role of statins in reducing the risk of AD
• Combined therapeutic approaches to AD
• Clinical trials in AD
• Future prospects of neuroprotection in AD
• Mild cognitive impairment
• Relation of MCI to AD
• Neuroprotection in MCI

9. Neuroprotection in Huntington Disease

• Introduction
• Pathophysiology of HD
• Management of Huntington's disease
• Neuroprotection in Huntington's disease
• Antipsychotic D2 and 5-HT1A antagonists
• Caspase inhibitors
• Clioquinol for HD
• Creatine for stabilizing bioenergetic defects
• Cysteamine
• Drugs that block inappropriate calcium release from neurons
• Enhancing protease activity for clearance of mHtt
• Eicosapentaenoic acid
• Free radical scavengers
• Histone deacetylase inhibitors
• Inhibitors of polyglutamine aggregation HD
• Pridopidine
• Simvastatin as a neuroprotective in HD
• Single chain Fv antibodies
• SIRT1 activators for neuroprotection in HD
• SIRT2 inhibitors for neuroprotection in HD
• Synaptic activation of NMDA receptors
• Tetrabenazine
• Combinatorial therapy and targeting multiple pathways in HD
• Cell transplants
• Neurotrophic factors and gene therapy
• RNAi therapy for Huntington's disease

10. Neuroprotection in Amyotrophic Lateral Sclerosis

• Introduction
• Pathophysiology of ALS
• Neuroprotective therapies for ALS
• Activated protein C
• AEOL 10150
• AIMSPRO
• Anakinra
• Arimoclomol for ALS
• Antisense therapy
• Creatine for ALS
• Ceftriaxone for ALS
• Coenzyme Q10 for ALS
• COX-2 inhibitors for ALS
• Dexpramipexole
• Diallyl trisulfide
• Erythropoietin for ALS
• Gene therapy for ALS
• Glatiramer acetate
• Insulin-like growth factor
• Ketogenic diet for neuroprotection in ALS
• Lenalidomide
• Lithium for neuroprotection in ALS
• Methylcobalamin
• Minocycline for ALS
• Olesoxime as neuroprotective for ALS
• ONO-2506 for ALS
• Riluzole
• RNAi-based therapy for ALS
• Sodium phenylbutyrate
• Stem cell therapy
• Talampanel
• Tamoxifen
• Vaccination for ALS caused by SOD1 mutations
• Vascular endothelial growth factor for ALS
• Vitamin E for ALS
• Clinical trials of neuroprotective therapies for ALS
• Concluding remarks and future prospects

11. Neuroprotection in Miscellaneous Neurological Disorders

• Introduction
• Age-related dementia
• Enhancing endogenous neurotrophic support of the aging brain
• Pharmacological approaches for treatment of age-related dementia
• Physical exercise to prevent decline of mental function with aging
• Vascular dementia
• Prediction of dementia in persons with vascular risk factors
• Management of subcortical vascular dementia
• Dementia with Lewy bodies
• Neuroprotection in AIDS dementia
• Multiple system atrophy
• Epilepsy
• Mechanisms of neuronal damage in epilepsy
• Strategies for neuroprotection in epilepsy
• Control of seizures by AEDs and neuroprotection
• Prevention of seizures by ketogenic diet
• Cell therapy for neuroprotection in epilepsy
• Cell therapy of posttraumatic epilepsy
• Cell therapy for temporal lobe epilepsy
• Cell therapy for pharmacoresistant epilepsies
• Gene therapy for neuroprotection in epilepsy
• Spinal and bulbar muscular atrophy
• Spinal muscular atrophy
• Multiple sclerosis
• Introduction
• Epidemiology of multiple sclerosis
• Pathophysiology
• Current management of multiple sclerosis
• Specific therapies for MS based on pathomechanism
• Neuroprotection in multiple sclerosis
• Clinical trials of neuroprotective therapies for MS
• Neuroprotection by control of progressive forms of multiple sclerosis
• Neuroprotection by controlling autoimmune inflammation in the brain
• Remyelination for neuroprotection in multiple sclerosis
• Agents for neuroprotection in multiple sclerosis
• Angiotensin-II inhibitors
• Antiglutamate agents
• Antioxidants for neuroprotection in MS
• Antisense and RNAi approaches to MS
• Cell therapy for multiple sclerosis
• Cladribine
• Dalfampridine in MS
• Dimethyl fumarate
• DNA vaccine for MS
• Erythropoietin as a neuroprotective in MS
• Fingolimod (FTY720)
• Fusokine composed of GM-CSF and IL-15 for immune suppression
• Gene therapy for MS
• Ibudilast for MS
• IVIG for MS
• Kinase inhibitors
• Laquinimod
• Monoclonal antibodies for MS
• Natalizumab
• Natural human antibodies for repair of myelin
• Neurotrophic factors for multiple sclerosis
• Oral immunomodulatory agents for MS
• Recombinant T-cell ligands
• Statins for MS
• Teriflunomide
• Concluding remarks on neuroprotection in MS
• Neuroprotection in transverse myelitis
• Neuroprotection in decompression sickness
• Neuroprotection in CSF circulatory disorders
• Neuroprotection in hydrocephalus
• Neuroprotection in normal pressure hydrocephalus
• Neuroprotection in infections of the CNS
• Neuroprotection in bacterial meningitis
• Mechanism of neural injury in bacterial meningitis
• Strategies for neuroprotection
• Neuroprotection in cryptococcal meningitis
• Neuroprotective approach to rabies
• Neuroprotection in cerebral malaria
• Neuroprotection in hypertensive encephalopathy
• Neuroprotection in toxic encephalopathies
• Hepatic encephalopathy
• Management of hepatic encephalopathy
• Encephalopathy due to organophosphorus poisoning
• Neuroprotection against chemotherapy-induced brain damage
• Neuroprotection against alcohol
• Alcoholic neurologic disorders
• Fetal alcohol syndrome
• Pathogenesis of alcohol-induced damage to the nervous system
• Neuroprotection against neurotoxicity of alcohol
• Neuroprotection in hypoxia-ischemia
• Neuroprotection in neonatal hypoxic-ischemic brain injury
• Minocycline for neonatal hypoxia-ischemia
• Nicotinamide mononucleotide adenylyl transferase 1
• Nitric oxide inhalation for neonatal hypoxia-ischemia
• Plasminogen activator inhibitor-1 for neonatal hypoxia-ischemia
• Recombinant erythropoietin for neonatal hypoxia-ischemia
• Neuroprotection in carbon monoxide poisoning
• Pathomechanism of CO poisoning as a basis for neuroprotection
• Management of CO poisoning
• Syndrome of delayed post-hypoxic leukoencephalopathy
• Neuroprotection of the fetus
• Neuroprotection in sleep apnea
• Neuroprotection in hypoglycemic coma
• Neuroprotection in mitochondrial dysfunction
• Mitochondrial permeability transition
• Mitochondrial approaches for neuroprotection
• Methylene blue
• Role of nanolasers in evaluation of mitochondrial neuroprotectants
• Neuroprotection in mitochondrial encephalopathies
• Neuroprotection in psychiatric disorders
• Cognitive impairment in schizophrenia
• Neuroprotection in schizophrenia
• Electroconvulsive therapy and neuroprotection
• Neuroprotection in hearing loss
• Causes of hearing loss
• Pathomechanism of hearing loss
• Prevention and treatment of hearing loss
• Hyperbaric oxygen for hearing loss
• Stem cell therapy for hearing loss
• Auditory hair cell replacement by gene therapy
• Pharmaceutical approaches to hearing loss
• Neuroprotection of peripheral nerves
• Neuroprotective agents for peripheral nerves
• Acetyl-L-carnitine for peripheral nerve injuries
• Atorvastatin for peripheral nerve injuries
• Erythropoietin for neuroprotection in peripheral nerve injuries
• Neuroprotection in peripheral nerve injuries
• Role of hyperbaric oxygen in peripheral nerve injuries
• Role of neurotrophic factors in peripheral nerve injuries
• Pharmacological approaches to Schwann cells
• Role of gene therapy in neuroprotection of injured peripheral nerves
• Schwann cell transplantation for peripheral nerve injury
• Peripheral neuropathy
• Neuroprotection in diabetic neuropathy
• Cell therapy for neuroprotection in diabetic neuropathy
• Gene therapy with zinc finger DNA-binding proteins
• Neuroprotection in chemotherapy-induced neuropathy
• Chronic inflammatory demyelinating polyradiculoneuropathy
• Neuroprotection in CIDP

12. Neuroprotection of the Optic nerve and the Retina

• Introduction
• Neuroprotection in optic neuropathy
• Neuroprotection in optic neuritis
• Neuroprotection in optic nerve trauma
• Potential regeneration of the optic nerve
• Subthreshold transpupillary thermotherapy for protection of RGCs
• Neuroprotection of optic nerve in glaucoma
• Aminoguanidine as a neuroprotective in glaucoma
• Antiglutamate agents for neuroprotection of optic nerve
• Betaxolol
• NGF eye drops
• Targeting Aβ in glaucoma treatment
• TNF-α blockers for neuroprotection in glaucoma
• Concluding remarks about neuroprotection in glaucoma
• Neuroprotection in retinal ischemia
• Endogenous neuroprotection in the retina
• β-adrenoceptor antagonists
• Brimonidine as a neuroprotective is ischemic retinopathy
• Thioredoxin as a neuroprotective agent in retinal ischemia
• Erythropoietin for neuroprotection of retinal ischemia
• Gene therapy for retinal neuroprotection
• Hyperbaric oxygen for central retinal artery occlusion
• Protection against oxygen-induced retinopathy
• Neuroprotection in macular degeneration
• Epidemiology
• Pathomechanism of AMD
• Current treatment of AMD
• Novel neuroprotective strategies against retinal degeneration
• Antiangiogenic agents
• Protection of retinal cells from oxidative-stress-induced apoptosis
• Nutritional protection against AMD
• Cell therapy for macular degeneration
• Retinal pigment epithelial cells
• Encapsulated cells delivering CNTF for geographical retinal atrophy
• Stem cells
• Neural progenitor cells
• Gene therapy for retinal degeneration
• RNAi-based treatments for AMD
• Neuroprotection in proliferative diabetic retinopathy
• Strategies for neuroprotection in diabetic retinopathy
• RNAi-based approaches to diabetic retinopathy
• Clinical trials for optic nerve and retinal neuroprotection

13. Neuroprotection during Anesthesia and Surgery

• Introduction
• Anesthetic agents as neuroprotectives
• Barbiturates
• Thiopental
• Etomidate
• Propofol
• Ketamine
• Gaseous anesthetics
• Isoflurane
• Xenon
• Local anesthetics
• Monitoring of CNS function during anesthesia and surgery
• Monitoring of cerebral function
• Monitoring of spinal cord function during spinal surgery
• Neuroprotection during cardiovascular procedures
• CNS complications of cardiac surgery
• Neuroprotective strategies during cardiac surgery
• Neuroprotection during coronary artery bypass grafting
• Neuroprotection before anticipated or induced cardiac arrest
• Surgery on the aorta
• Spinal cord protection during cardiovascular surgery
• Cerebral protection during organ transplantation surgery
• Cerebral protection during neurosurgery
• Cerebral angiography and endovascular surgery
• Cerebral protection during surgery for arteriovenous malformations
• Cerebral protection during surgery of intracranial aneurysms
• Management of subarachnoid hemorrhage
• Vasospasm associated with subarachnoid hemorrhage
• Cerebral protection during carotid endarterectomy
• Cerebral protection during surgery of brain tumors
• Neuroprotective measures prior to surgery
• Neuroprotection following surgery

14. Commercial Aspects of Neuroprotective Therapies

• Introduction
• The financial burden of CNS damage
• Markets for neuroprotective therapies
• Markets according to therapeutic areas
• Values of neuroprotective therapies in major world markets
• Unmet needs in neuroprotectives
• Future prospects of neuroprotective therapies
• Challenges in neuroprotective drug development
• Promising areas of research in neuroprotection
• Autoreactive antibodies
• Biological therapies for neuroprotection
• Multidisciplinary approaches to neuroprotection

15. References

Tables

• Table 1 1: Historical landmarks in the development of neuroprotection
• Table 1 2: Intrinsic neuroprotective factors
• Table 1 3: Common features of pathophysiology of brain damage in diseases
• Table 1 4: Place of neuroprotection in management of CNS disorders
• Table 1 5: Indications for the use of neuroprotection
• Table 2 1: A classification of neuroprotective agents
• Table 2 2: The neuroprotective effect of antiepileptic drugs
• Table 2 3: Neuroprotective affect of minocycline in animal models
• Table 2 4: Classification of antioxidants or free radical scavengers with neuroprotective potential
• Table 2 5: Role of erythropoietin in the nervous system
• Table 2 6: Ionotropic glutamate receptors
• Table 2 7: Classification of metabotropic glutamate receptors (mGluRs)
• Table 2 8: Methods for neuroprotection based on nonpharmacological preconditioning
• Table 3 1: Cerebrovascular diseases that are relevant to neuroprotection
• Table 3 2: Neuroprotective strategies for stroke
• Table 3 3: Neuroprotective gene transfer in models of cerebral ischemia
• Table 3 4: Neuroprotective gene therapy in animal stroke models
• Table 3 5: Neuroprotective agents in clinical development for acute cerebrovascular disease
• Table 3 6: Some failed trials for neuroprotective therapy for stroke
• Table 3 7: Preclinical assessment of neuroprotective agents in acute stroke models
• Table 4 1: Current conventional management of traumatic brain injury
• Table 4 2: Neuroprotective strategies for traumatic brain injury
• Table 4 3: Ongoing or completed clinical trials for neuroprotection in TBI
• Table 4 4: Discontinued or failed clinical trials for neuroprotection in TBI
• Table 5 1: Secondary mechanisms in spinal cord injury
• Table 5 2: Neuroprotective and regenerative approaches for SCI
• Table 5 3: Clinical trials for neuroprotection in SCI
• Table 6 1: Glutamate-based therapies in clinical development for neurodegenerative disorders
• Table 7 1: Prevalence of Parkinson's disease in major markets 2011-2021
• Table 7 2: Factors in the etiology of Parkinson's disease
• Table 7 3: Strategies for the treatment of Parkinson's disease
• Table 7 4: Current clinical trials of neuroprotective therapies for Parkinson disease
• Table 7 5: Failed clinical trials of neuroprotective therapies for Parkinson disease
• Table 7 6: Evaluation of neuroprotective agents for PD
• Table 8 1: Cholinergic approaches to the treatment of Alzheimer's disease
• Table 8 2: Neuroprotective agents for Alzheimer's disease
• Table 8 3: Clinical trials for neuroprotection in Alzheimer disease
• Table 8 4: Discontinued, failed or inconclusive clinical trials of Alzheimer disease
• Table 8 5: Strategies for discovery of neuroprotective therapies for AD
• Table 9 1: Neuroprotective approaches in HD
• Table 10 1: Classification of neuroprotective agents for amyotrophic lateral sclerosis
• Table 10 2: Clinical trials of neuroprotective therapies for ALS
• Table 10 3: Failed or discontinued trials of neuroprotective therapies for ALS
• Table 11 1: Therapeutic approaches to subcortical vascular dementia
• Table 11 2: Pharmacological neuroprotection against the sequelae of seizures
• Table 11 3: Neuroprotective effect of AEDs in animal models of status epilepticus (SE)
• Table 11 4: Specific therapies for MS based on postulated pathomechanisms
• Table 11 5: Approved neuroprotective therapies for multiple sclerosis
• Table 11 6: Neuroprotective therapies for multiple sclerosis in clinical trials
• Table 11 7: Failed or discontinued trials of neuroprotective therapies for ALS
• Table 11 8: Approaches to neuroprotection in neonatal hypoxia-ischemia
• Table 11 9: Drugs with neuroprotective effect at mitochondrial level
• Table 11 10: Causes of sensorineural hearing impairment
• Table 11 11: Strategies for prevention and treatment of sensorineural hearing loss
• Table 11 12: Agents for neuroprotection of the peripheral nervous system
• Table 12 1: Causes of optic neuropathy
• Table 12 2: Neuroprotection of the optic nerve in glaucoma
• Table 12 3: Strategies for neuroprotection in retinal ischemia
• Table 12 4: Novel neuroprotective strategies against retinal degeneration
• Table 12 5: Clinical trials for optic nerve and retinal neuroprotection
• Table 13 1: CNS complications associated with cardiac procedures
• Table 13 2: Strategies for protection of the brain during cardiac surgery
• Table 13 3: Medical and surgical methods of cerebral vasospasm management
• Table 13 4: Neuroprotection by prevention of vasospasm
• Table 14 1: Neuroprotective market values 2011-2021
• Table 14 2: Values of neuroprotective therapies in major world markets from 2011-21

Figures

• Figure 2 1: Mechanism of neuroprotective effect of sigma-1 receptor agonists
• Figure 2 2: NMDA receptor ion channel complex
• Figure 2 3: Neuroprotective effect of galantamine
• Figure 3 1: Some steps in the ischemic cascade and site of action of neuroprotectives
• Figure 3 2: A roadmap for neuroprotection
• Figure 4 1: Cascade of events following traumatic brain injury
• Figure 5 1: Pathomechanism of acute spinal cord injury
• Figure 7 1: Neuroprotective strategies against death of dopamine-containing neurons in PD
• Figure 11 1: Common mechanisms of neural damage in cerebral ischemia and seizures
• Figure 11 2: Role of neuroprotection in epilepsy and its treatment
• Figure 8 1: Unmet therapeutic needs in neuroprotective therapies

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