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SUMMARY
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 95 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 in stroke and head
injury are analyzed with suggestions for improving the selection of drugs and
design of trials.The report is supplemented with 63 tables and 10 figures.
Market analysis of currently used productsthat have a neuroprotective effect
are analyzed for the year 2007. 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 2012 when it will
constitute a major and important component of the CNS market. Forecasts are
made until 2017. 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
- Neurotrophic factors
- Intrinsic non-enzymatic antioxidants
- Intrinsic neuroprotective proteins
- Excitatory amino acid transporters (EAATs)
- Extracellular serine protease thrombin
- Neuroglobin
- Galanin
- Prion protein
- Rai (Shc C) adaptor protein
- Stem cell factor
- Role of the immune system in 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
- Brain-on-a-Chip™ technology
- Role of brain imaging in neuroprotective drug discovery and development
- 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
- Evaluation of neuroprotective effect of drugs approved for other
indications
2. Neuroprotective Agents
- Classification of neuroprotective agents
- Activated protein C
- Activity-dependent neuroprotective protein
- Adenosine analogs
- Andepressants
- Antiepileptic drugs as neuroprotectives
- Phenytoin
- Valproic acid
- Levetiracetam
- Antiinflammatory agents
- Aspirin
- Interleukin-1 antagonists
- COX-2 inhibitors
- Minocycline
- VP015
- Anti-apoptosis agents
- Activated protein C
- Calpain inhibitors
- Caspase inhibitors
- Clusterin
- DNA binding drugs
- Lithium
- Omega-3 fatty acids
- Poly (ADP-ribose) polymerase (PARP) inhibitors
- Prevention of apoptosis by binding of proNGF to Sortilin
- TRO19622
- 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
- Carbon monoxide and heme oxygenase
- Cell transplants
- Cells secreting neuroprotective substances
- Stem cells
- Cytokines
- Erythropoietin
- Non-erythropoietic EPO variants and mimics
- Granulocyte colony-stimulating factor
- Delta-opioid receptor agonists
- FK960
- GABA agonists
- 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
- Glycine-proline-glutamate analogs
- Herbal preparations
- Flavonoid wogonin
- Ginseng
- NMDA receptor ion channel complex
- NMDA receptor antagonists
- NPS 1506
- NMDA NR2B subunit receptor antagonists
- Ifenprodil
- Memantine
- Magnesium
- NAALADase inhibitors
- 3,3-bis (3-fluorophenyl) propylamine
- Gacyclidine (GK-11)
- N-alkylglycines
- Partial NMDA agonists at glycine site
- AMPA receptor modulators
- Metabotropic glutamate receptor modulators
- Cannabinoids
- Dexanabinol (HU-211)
- Glutathione
- Heat shock proteins
- Hormones
- Estrogen and neuroprotection
- Neuroprotective effect of estrogen receptor ligands
- Selective estrogen receptor modulators
- Receptor-independent neuroprotective effects of estrogens
- Mitochondrial mechanisms of estrogen neuroprotection
- Insulin
- Ion Channel modulators
- Calcium channel blockers
- Na+ channel blockers
- Neuroprotective potassium channel inhibitors
- Kynurenine inhibitors
- Leukocyte adhesion inhibitors
- Modafinil
- Neural regeneration protein
- Neurite outgrowth-promoting prostaglandin compounds
- Neuroimmunophilins
- Cyclosporin
- FK506
- GPI 1485
- Rapamycin
- Neuropeptides
- Corticotropin-releasing hormone
- Neuroprotective peptide NAP
- Thyrotropin-releasing hormone
- Vasoactive intestinal peptide (VIP)
- 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-β1
- Vascular endothelial growth factor
- Neurotrophic factor-related neuroprotective agents
- Colivelin
- Gambogic amide
- Inosine
- Meteorin
- Oxygen-regulated protein 150 kD (ORP150)
- Prosaptide
- Siagoside (GM1 ganglioside)
- Nicotine and nicotinic receptor agonists
- Nitric oxide-based neuroprotection
- Nitric oxide synthase inhibitors
- Nitric oxide mimetics
- Nootropics
- Nutraceuticals and food constituents
- Creatine
- Curcumrin/ curry
- Glyceryltriacetate
- Green tea
- Nicotinamide
- Resveratrol/red wine
- Osmotic diuretics
- Mannitol
- Osteopontin
- Oxygen therapeutics
- Oxygen carriers
- Hemoglobin-based oxygen carriers
- Perfluorocarbons as oxygen carriers
- Hyperbaric oxygen therapy
- PPARs as drug targets for neuroprotection
- Riluzole
- Role of RNA interference in neuroprotection
- Signaling pathway activator
- Fructose-1,6-bisphosphate
- Sir 2 group of proteins
- Statins
- Steroids
- Dehydroepiandrosterone
- HF0220
- Sulforaphane
- Tauroursodeoxycholic acid
- Tetanus toxin as a neuroprotective agent
- Uncoupling protein 2
- Vaccines as neuroprotectives
- Vitamins as neuroprotective agents
- Non-pharmacological approaches to neuroprotection
- Environmental enrichment
- Hypothermia
- Limitations of hypothermia
- Hypothermic neuroprotection in hypoxia-ischemia
- Hibernation induced by hydrogen sulfide
- Ketogenic diet
- Preconditioning-induced neuroprotection
- Hypoxic preconditioning
- Moderate stimulation of reactive oxygen species
- Chemical preconditioning
- 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
- Epidemiology of stroke
- Pathophysiology of cerebral ischemia
- Calcium overload
- Ion channel dysfunction in stroke
- Role of oxygen free radicals in cerebral ischemia
- Role of Nitric oxide (NO) in cerebral ischemia
- Glutamate as a marker 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 (TNF)-α
- Interleukin (IL)-1 and IL-6
- Adhesion molecules
- DNA damage and repair in cerebral ischemia
- Role of neurotrophic factors
- 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
- Neuroprotective therapies for stroke
- Agents in research/preclinical stage for neuroprotection in stroke
- Acid-sensing ion channel blockers
- AMPA receptor antagonists as neuroprotectives for stroke
- Anti-apoptotic neuroprotectives
- NIM811
- Creatine as neuroprotective in stroke
- Lithium as a neuroprotective in stroke
- TUDCA as a neuroprotective in stroke
- Anti-HMGB1 monoclonal antibody
- Antioxidant approaches
- Dehydroascorbic acid
- Tocotrienols
- Carnosine as a neuroprotective in stroke
- Antiglutamate compounds
- 202W92
- AR-R15896AR
- MRZ 2/576
- L-Phenylalanine
- Arimoclomol for stroke
- Cardiac glycosides as neuroprotectives in stroke
- Clenbuterol
- Cox-2 inhibitors for ischemic stroke
- Enoxaparin
- Estrogen for stroke
- Granulocyte-macrophage colony-stimulating factor for cerebral ischemia
- Histamine H2-receptor antagonists
- Inosine for stroke
- Intravenous immunoglobulin as neuroprotective in stroke
- Insulin-like growth factor-I
- Ischemic preconditioning for neuroprotection in stroke
- Ketone bodies
- Minalocorticoid receptor blockade for neuroprotection
- Multifunctional neuroprotective agents
- Neuroserpin as a neuroprotective in stroke
- N-2-mercaptopropionyl glycine
- NeuroAid
- Neurotrophic factors as neuroprotectives for stroke
- AX200
- Brain-derived neurotrophic factor
- Neuregulin-1
- NO-based strategies for neuroprotection in cerebral ischemia
- Peroxisome proliferator-activated receptor-γ agonists
- PGE2 EP2 receptor activation
- Pioglitazone for reduction of stroke risk in diabetes
- Progesterone
- Proteosome inhibitors
- Statins for stroke prevention
- Thrombosis inhibitors
- Aspirin
- Clopidogrel
- Dipyridamole
- CBL1309
- SB-239063
- Sildenafil
- Src receptor blockade
- Stroke vaccine
- SUN N4057
- Tiagabine
- Topiramate
- Zonisamide
- Neuroprotectives in reperfusion injury
- 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
- Role of neurosurgical procedures for neuroprotection in stroke
- Neurorehabilitation in relation to neuroprotection in stroke
- Cell therapy for stroke
- Gene therapy for neuroprotection in cerebrovascular disease
- Neuroprotective genetic vaccine
- COX-1/PGIS and COX-1 gene transfer in cerebral ischemia
- Transfer of the bcl-2 gene for neuroprotection in cerebral ischemia
- Neuroglobin gene therapy
- Neuroprotective therapies for cerebral ischemia: clinical trials
- Albumin
- Free radical scavengers
- DP-b99
- Erythropoietin as a neuroprotective in stroke
- MaxiPost (BMS-204352)
- Minocycline for neuroprotection in stroke
- Failed clinical trials of neuroprotection in stroke
- Aptiganel
- Cerovive (NXY-059)
- Desmoteplase
- SPD 502
- Tirilazad mesylate
- Selfotel (CGS 19755)
- Lubeluzole
- Nalmefene (Cervene)
- Gavestinel (GV150526)
- Nimodipine
- Repinotan
- 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 CNS Trauma
- Introduction
- Cerebral hypoxia/ischemia as a complication of trauma
- Traumatic brain injury (TBI)
- 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
- Changes in neurotrophic factors following TBI
- Changes in neurotransmitters following 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
- Beta blockers
- Bradykinin B2 antagonists
- Cell cycle inhibitors for TBI
- Creatine for neuroprotection in 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
- Magnesium sulfate
- Neurotrophic factors for TBI
- Neurosteroids as neuroprotective agents for TBI
- NMDA receptor antagonists
- Non-NMDA receptor antagonists
- Nogo-A inhibitor
- Omega 3 fatty acids as neuroprotectives in TBI
- Oxygen carriers for TBI
- Polyethylene glycol for neuroprotection in TBI
- Propofol for neuroprotection in TBI
- Rapamycin as neuroprotective in TBI
- Thyrotropin-releasing hormone analogs
- Traxoprodil
- Antisense approaches to TBI
- Cell therapy for TBI
- Gene therapy for TBI
- Vaccine for TBI
- Hyperbaric oxygen therapy for TBI
- Hypothermia
- Reduction of microglial migration after TBI
- Deep brain stimulation for TBI
- Clinical trials of neuroprotective agents 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 multipotential treatment strategies
- Shortening the trial time
- Concluding remarks and future prospects of neuroprotection in TBI
- Acute spinal cord injury (SCI)
- Epidemiology of SCI
- Pathophysiology of SCI
- Secondary mechanisms of SCI
- Neurotrophic factor changes in SCI
- Management of SCI
- Pharmacological neuroprotective agents for SCI
- 4-aminopyridine(4-AP, famprodine)
- Antibodies as neurite growth inhibitors in SCI
- Bacterial enzyme chondroitinase ABC
- CRL-5861
- 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
- Matrix metalloproteinase inhibitors for SCI
- Methylprednisolone
- Minocyline as neuroprotective in SCI
- Neurotrotrophic factors for neuroprotection after SCI
- Rho pathway and Rho antagonists in SCI
- Selenium as a neuroprotective for 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 and gene therapy for SCI
- Cell transplants
- Gene therapy for SCI
- Combined approaches to spinal cord injury
- Discovery of new targets for neuroprotective therapies in SCI
- Clinical trials in SCI
5. Neuroprotection in Neurodegenerative Disorders
- Introduction
- Pathomechanism of neurodegeneration
- Lack of neurotrophic factors
- Dual role of α synuclein in neuroprotection and neurodegeneration
- Role of apoptosis in neurodegenerative disorders
- Role of glia in neurodegeneration
- Role of metals in neurodegeneration
- Role of neuroinflammation in neurodegenerative disorders
- Modulation of neurodegeneration by molecular chaperones
- Targeting aggregation-prone regions in proteins to prevent amyloid
formation
- Glutamate-based therapies for neurodegenerative disorders
- Parkinson's disease
- 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 Parkinson's disease
- Neuroprotective therapy in Parkinson's disease
- Neuroprotective effect of currently used drugs for Parkinson's disease
- Pramipexole
- Rasagiline mesylate
- Ropinirole
- Selegiline
- Free radical scavengers for neuroprotection in Parkinson's disease
- Antioxidants
- Melatonin
- Tea extracts as neuroprotectives
- Nicotine as a neuroprotective in PD
- Non-pharmacological strategies for neuroprotection in Parkinson's disease
- Preventive effect of exercise and environmental enrichment
- Low-calorie diet
- Research in neuroprotection for Parkinson's disease
- Activation of the hedgehog signaling pathway
- Activation of endogenous stem cells by D3 receptor agonists
- Adenosine AA2 receptor antagonists
- Anti-apoptotic strategies for PD
- Conserved dopamine neurotrophic factor for PD
- Heat shock protein 70 (Hsp70)
- Neuroprotective effect of DJ-1 protein
- Omega-3 polyunsaturated fatty acids
- Sirtuin 2 inhibitors for neuroprotection in PD
- Statins and PD
- Targeting Bax
- Tobacco smoke constituents
- Synergistic effect of dopamine and cannabinoid agonists in PD
- Clinical trials of neuroprotection in Parkinson's disease
- CEP-1347
- Creatine and minocycline
- Neurotrophic factors
- PYM50028
- Safinamide
- Cell therapies
- Gene therapy
- RNAi therapy for Parkinson's disease
- Vaccine for PD
- Future challenges for neuroprotection in PD
- Evaluation of neuroprotective therapies for PD
- Alzheimer's 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 amyloid β-protein aggregation
- Secretase inhibitors
- AN-1792
- Monoclonal antibody m266
- Inhibition of the transformation of spherons into amyloid plaques
- Clioquinol
- FKBP52 for neuroprotection from Cu toxicity in AD
- Phenserine
- Colostrinin
- Inhibition of neuroinflammation by MW01-5-188WH
- Neurotrophic factors/ gene therapy
- NGF gene therapy
- Neotrofin (leteprinim potassium, AIT-082)
- AL-108
- Targeting plasminogen activator inhibitor type-1 gene
- Estrogen
- ABS-205
- Nimodipine
- Antioxidants
- Memantine
- Dimebon
- Cerebrolysin
- Ginko biloba
- Tetrahydrocannabinol for neuroprotection in AD
- CPI-1189
- Ladostigil tartrate
- Phosphodiesterase inhibitors
- PPAR-γ gamma agonists
- Role of statins in reducing the risk of Alzheimer's disease
- Combined therapeutic approaches to Alzheimer's disease
- Clinical trials in Alzheimer's disease
- Future prospects of neuroprotection in AD
- Huntington's disease
- Epidemiology of HD
- Pathophysiology of HD
- Management of Huntington's disease
- Neuroprotection in Huntington's disease
- Free radical scavengers
- Inhibitors of polyglutamine aggregation HD
- Enhancing protease activity for clearance of mHtt
- Eicosapentaenoic acid
- Single chain Fv antibodies
- Creatine for stabilizing bioenergetic defects
- Caspase inhibitors
- Clioquinol for HD
- Drugs that block inappropriate calcium release from neurons
- Histone deacetylase inhibitors
- Antipsychotic D2 and 5-HT1A antagonists
- Tetrabenazine
- Combinatorial therapy and targeting multiple pathways in HD
- Cell transplants
- Neurotrophic factors and gene therapy
- RNAi therapy for Huntington's disease
- Amyotrophic lateral sclerosis (ALS)
- Epidemiology of ALS
- Pathophysiology of ALS
- Neuroprotective therapies for ALS
- AEOL 10150
- Arimoclomol for ALS
- Antisense therapy
- Ceatine for ALS
- Ceftriaxone for ALS
- Coenzyme Q10 for ALS
- COX-2 inhibitors for ALS
- Gene therapy for ALS
- Glatiramer acetate
- Ketogenic diet for neuroprotection in ALS
- Lithium for neuroprotection in ALS
- Minocycline for ALS
- Neurotrophic factors for ALS
- ONO-2506 for ALS
- Riluzole
- RNAi-based therapy for ALS
- Sodium phenylbutyrate
- Stem cell therapy
- Talampanel
- Tamoxifen
- TRO19622 as neuroprotective for ALS
- Vaccination for ALS caused by SOD1 mutations
- Status of development of neuroprotective therapies for ALS
- Concluding remarks and future prospects of neuroprotection in ALS
6. Neuroprotection in Miscellaneous Neurological Disorders
- Dementias due to miscellaneous causes
- 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
- A test for prediction of dementia in persons with vascular risk factors
- Management of vascular dementia
- Dementia with Lewy bodies
- Creutzfeldt-Jakob disease
- TDP-43 proteinopathy and neurodegenerative diseases
- Genetic disorders with neurodegeneration
- Niemann-Pick type C disease
- Friedrich's ataxia
- Epilepsy
- Mechanisms of neuronal damage in epilepsy
- Strategies for neuroprotection in epilepsy
- Control of seizures and neuroprotection
- Responsive Neurostimulator System
- Neuroprotective effect of estrogens in epilepsy
- Cell therapy for neuroprotection in epilepsy
- Gene therapy for neuroprotection in epilepsy
- Multiple sclerosis
- Introduction
- Epidemiology of multiple sclerosis
- Pathophysiology
- Current management of multiple sclerosis
- Specific therapies for MS based on pathomechanism
- Neuroprotection in multiple sclerosis
- Neuroprotection by control of progressive forms of multiple sclerosis
- Neuroprotective role of inflammation in multiple sclerosis
- 4-aminopyridine(4-AP, fampridine) in MS
- Antiglutamate agents
- Antioxidants for neuroprotection in MS
- Antisense and RNAi approaches to MS
- Cell therapy for multiple sclerosis
- Cladribine
- Dexanabinol for MS
- DNA vaccine for MS
- Erythropoietin as a neuroprotective in MS
- Fingolimod (FTY720)
- Gene therapy for MS
- IVIG for MS
- Laquinimod
- MBP8298
- Monoclonal antibodies for MS
- Natalizumab
- Natural human antibodies for repair of myelin
- Neurotrophic factors for multiple sclerosis
- Recombinant T-cell ligands
- Statins for MS
- Concluding remarks on neuroprotection in MS
- Chronic inflammatory demyelinating polyradiculoneuropathy
- Neuroprotection in transverse myelitis
- 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 AIDS
- AIDS dementia
- Role of neurotrophic factors in AIDS dementia
- Neuroprotection in AIDS dementia
- Neuroprotective approach to rabies
- Neuroprotection in cerebral malaria
- Neuroprotection in toxic encephalopathies
- 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 sleep apnea
- Neuroprotection in hypoglycemic coma
- Neuroprotection in neonatal hypoxic-ischemic brain injury
- Neuroprotection in mitochondrial dysfunction
- Mitochondrial permeability transition
- Methylene blue
- Role of nanolasers in evaluation of mitochondrial neuroprotectants
- Neuroprotection in mitochondrial encephalopathies
- Neuroprotection in schizophrenia
- Neuroprotection of the optic nerve and the retina
- Neuroprotection in optic nerve trauma
- Potential regeneration of the optic nerve
- Neuroprotection of optic nerve in glaucoma
- Aminoguanidine as a neuroprotective in glaucoma
- Antiglutamate agents for neuroprotection of optic nerve
- Axonal growth factors for neuroprotection of the optic nerve
- Betaxolol
- Targeting Aβ in glaucoma treatment
- 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
- Neuroprotection in macular degeneration
- Anti-angiogenic agents
- Protection of retinal cells from oxidative-stress-induced apoptosis
- Nutritional protection against AMD
- Cell therapy for macular degeneration
- Gene therapy for retinal degeneration
- RNAi-based treatments for AMD
- Neuroprotection in proliferative diabetic retinopathy
- Companies developing products for retinal neuroprotection
- Neuroprotection in hearing loss
- Neuroprotection of peripheral nerves
- Neuroprotection in diabetic neuropathy
- Neuroprotection in chemotherapy-induced neuropathy
7. Neuroprotection during Anesthesia and Surgery
- Introduction
- Anesthetic agents as neuroprotectives
- Barbiturates
- Etomidate
- Propofol
- Ketamine
- Gaseous anesthetics
- Local anesthetics
- Monitoring of CNS function during anesthesia and surgery
- Monitoring of cerebral function
- Monitoring of spinal cord function during surgery on the spine
- 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 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
- Neuroprotection during spinal surgery
- Neuroprotective measures prior to surgery
8. Commercial aspects of Neuroprotective Therapy
- 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
- Protective genes
9. 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 antiodixants 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 preconditioning-induced neuroprotection
- Table 3 - 1: Cerebrovascular diseases that are relevant to neuroprotection
- Table 3 - 2: Neuroprotective strategies for stroke
- Table 3 - 3: Pharmacological products in research/preclinical stage for
stroke
- 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 4 - 5: Secondary mechanisms in spinal cord injury
- Table 4 - 6: Neuroprotective and regenerative approaches for SCI
- Table 4 - 7: Clinical trials for neuroprotection in SCI
- Table 5 - 1: Glutamate-based therapies in clinical development for
neurodegenerative disorders
- Table 5 - 2: Prevalence of Parkinson's Disease in major markets 2005-2015
- Table 5 - 3: Factors in the etiology of Parkinson's disease
- Table 5 - 4: Strategies for the treatment of Parkinson's disease
- Table 5 - 5: Neuroprotective therapies in preclinical development for
Parkinson's disease
- Table 5 - 6: Current clinical trials of neuroprotective therapies for
Parkinson's disease
- Table 5 - 7: Failed clinical trials of neuroprotective therapies for
Parkinson's disease
- Table 5 - 8: Evaluation of neuroprotective agents for PD
- Table 5 - 9: Cholinergic approaches to the treatment of Alzheimer's disease
- Table 5 - 10: Neuroprotective agents for Alzheimer's disease
- Table 5 - 11: Clinical trials in Alzheimer disease
- Table 5 - 12: Discontinued, failed or inconclusive clinical trials of
Alzheimer disease
- Table 5 - 13: Strategies for discovery of neuroprotective therapies for AD
- Table 5 - 14: Neuroprotective approaches in HD
- Table 5 - 15: Classification of neuroprotective agents for amyotrophic
lateral sclerosis
- Table 5 - 16: Clinical trials of neuroprotective therapies for ALS
- Table 5 - 17: Failed or discontinued trials of neuroprotective therapies
for ALS
- Table 6 - 1: Therapeutic approaches to vascular dementia
- Table 6 - 2: Pharmacological neuroprotection against the sequelae of
seizures
- Table 6 - 3: Neuroprotective effect of AEDs in animal models of status
epilepticus (SE)
- Table 6 - 4: Specific therapies for multiple sclerosis based on postulated
pathomechanisms
- Table 6 - 5: Neuroprotective therapies for multiple sclerosis
- Table 6 - 6: Drugs with neuroprotective effect at mitochondrial level
- Table 6 - 7: Neuroprotection of the optic nerve in glaucoma
- Table 6 - 8: Strategies for neuroprotection in retinal ischemia
- Table 6 - 9: Novel neuroprotective strategies against retinal degeneration
- Table 6 - 10: Companies developing products for retinal neuroprotection
- Table 7 - 1: CNS complications associated with cardiac procedures
- Table 7 - 2: Neuroprotective strategies for cardiac surgery
- Table 7 - 3: Medical and surgical methods of cerebral vasospasm management
- Table 7 - 4: Neuroprotection by prevention of vasospasm
- Table 8 - 1: Neuroprotective market values 2007-2017
- Table 8 - 2: Values of neuroprotective therapies in major world markets
from 2007-2017
Figures
- Figure 2 - 1: NMDA receptor ion channel complex
- Figure 2 - 2: 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 4 - 2: Pathomechanism of acute spinal cord injury
- Figure 5 - 1: Neuroprotective strategies against death of
dopamine-containing neurons in PD
- Figure 6 - 1: Common mechanisms of neural damage in cerebral ischemia and
seizures
- Figure 6 - 2: Role of neuroprotection in epilepsy and its treatment
- Figure 8 - 1: Unmet therapeutic needs in neuroprotective therapies
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