Reportlinker Adds Alzheimer Disease - New Drugs, Markets and Companies
NEW YORK, June 3 /PRNewswire/ -- Reportlinker.com announces that a new market research report is available in its catalogue:
Alzheimer disease - new drugs, markets and companies
http://www.reportlinker.com/p0203533/Alzheimer-disease---new-drugs-markets-and-companies.html
Summary
Alzheimer's disease remains a challenge in management. With nearly 8 million sufferers from this condition in the seven major markets of the world and anticipated increases in the future. Considerable research is in progress to understand the pathomechanism of the disease and find a cure. The only drugs approved currently are acetylcholinesterase inhibitors but they do not correct the basic pathology of the disease, beta amyloid deposits and neurofibrillary tangles. Several new approaches emphasize neuroprotection as well.
Early diagnosis of Alzheimer's disease is an important first step in management. Several biomarkers in cerebrospinal fluid, blood and urine can detect the disease. They provide a valuable aid to the clinical examination and neuropsychological testing which are the main diagnostic methods supplemented by brain imaging. Genotyping, particularly of ApoE gene alleles is also useful in the evaluation of cases and planning management.
The current management of Alzheimer's disease is reviewed and it involves a multidisciplinary approach. Acetylcholinesterase inhibitors are mostly a symptomatic treatment but some claims are made about a neuroprotective effect. Currently the only approved neuroprotective therapy in is memantine. Management of these patients also require neuroleptics for aggressive behavior and antidepressants. There is an emphasis on early detection at the stage of mild cognitive impairment and early institution of neuroprotective measures. The value of mental exercise in delaying the onset of Alzheimer's disease is being recognized.
Research in Alzheimer's disease still aims at elucidating the basic pathomechanisms. Animal models are important for research, particularly in testing some of the potential therapeutic approaches. There is considerable research in progress at the various centers, some of which is funded by the National Institute of Aging of the National Institutes of Health.
Over 300 different compounds are at various stages of development for the treatment of Alzheimer's disease. These are classified and described. There are non-pharmacological approaches such as vagal nerve stimulation and cerebrospinal fluid shunting, which are in clinical trials. Over 171 clinical trials are listed, of which 127 are still in progress and 44 were discontinued for various reasons.
Alzheimer's disease market in the seven major markets is analyzed for the year 2008. Several new therapies are expected to be in the market and the shares of various types of approaches are estimated for the future up to the year 2018. As a background to the markets, pharmacoeconomic aspects of care of Alzheimer disease patients and patterns of practice are reviewed in the seven major markets.
Profiles of 139 companies involved in developing diagnostics and therapeutics for Alzheimer's disease are presented along with 104 collaborations. The bibliography contains over 600 publications that are cited in the report. The report is supplemented with 42 tables and 14 figures.
TABLE OF CONTENTS
0. Executive Summary 17
1. Clinical Features, Epidemiology and Pathology 19
Introduction 19
Historical aspects 19
Clinical features of Alzheimer disease 20
Seven stages of Alzheimer disease 22
AD as a terminal illness 24
Detection of AD in the preclinical phase 24
Differentiation of AD from other dementias 24
Differentiation of AD from non-dementing disorders 25
Cerebral insufficiency and AD 26
Memory deficits and preclinical AD 26
Mild cognitive impairment 27
Diagnostic criteria of AD 28
Epidemiology 30
Epidemiology of aging 30
Epidemiology of dementia 31
Epidemiology of AD 31
Prevalence of AD according to age 32
Mortality in AD 32
Pathophysiology of AD 33
Cerebral atrophy and neuronal loss 33
Neuritic plaques and neurofibrillary tangles 33
Sp proteins as markers of neuronal death in AD 34
Role of tau in the pathogenesis of AD 34
Amyloid precursor protein 35
Relation of APP mutations to CNS disorders 35
Relation of APP to A? deposits and pathogenesis of AD 36
APP intracellular domain 37
Role of secretases in amyloid cascade 38
Role of exosomal proteins 40
Role of nicastrin 40
Neurotixicity of A? deposits 40
Relation of A? deposits to synaptic activity 40
Dysfunction of TGF-? signaling accelerates A? deposition 41
Role of TMP21 in presenilin complexes and A? formation 41
Role of A? dimers in the pathogenesis of AD 42
Structure–neurotoxicity relationships of A? oligomers 42
A? deposit and clearance 42
Impairment of mitochondrial energy metabolism 43
A?-binding alcohol dehydrogenase links AD to mitochondrial toxicity 44
Neural thread protein 44
Loss of synaptic proteins 44
AD and Down syndrome 45
Overlapping pathologies of AD and Parkinson disease 45
AD and age-related macular degeneration 46
Myelin hypothesis of AD 46
Blood-brain barrier in AD 46
Blood vessel damage in AD 48
Loss of serotonin 1A receptors in the brain 48
Factors in pathogenesis of AD 48
Astrocytes and AD 48
Axonal transport failure in AD 49
Cell-cycle hypothesis 49
Chronic heart failure link with AD 49
Creatine and AD 50
Disturbances of interaction of nervous system proteins 50
DENN/MADD expression and enhanced pro-apoptotic signaling in AD 50
Gonadotrophins and AD 50
Glutamate transport dysfunction in AD 51
Innate immune system and AD 52
Insulin, diabetes and AD 52
Mechanisms underlying cognitive deficits in AD 53
Monoamine oxidase and AD 54
Neuroinflammation and AD 54
Neurotransmitter deficits 55
Neurotrophic factors 55
NF-?B signaling and the pathogenesis of neurodegeneration 56
Nitric oxide and AD 56
Nogo receptor pathway 59
Oxidative stress and AD 59
Prostaglandins and AD 61
Quinolinic acid and AD 61
Retromer deficiency 61
Serotonin and AD 62
Spherotoxin 62
Synaptic failure in AD 62
Transmission of AD 63
Ubiquitin-proteasome system in pathogenesis of AD 63
Risk factors in the etiology of AD 64
Aging and developmental abnormalities of the cholinergic system 65
Cholesterol, dietary lipids, and A? 65
Exposure to magnetic fields 66
Family history of AD 66
Homocysteine and AD 66
Level of education/type of job and risk of AD 67
Metals and AD 68
Obesity 69
Proneness to psychological distress and risk of AD 70
Reduced muscle strength 70
Sleep deprivation 70
Traumatic brain injury and AD 71
Vascular risk factors for AD 72
Vitamin B12 and folate 73
AD versus non-dementing changes in the aging brain 73
AD and cognitive impairment with aging 74
Pathomechanism of memory impairment and AD 74
Concluding remarks on pathophysiology of AD 75
Genetics of AD 76
Familial AD 76
Presenilins and calcium channel leak in pathogenesis of familial AD 78
Late onset AD 78
Genomics of AD 78
Introduction to genomics 78
Genes associated with Alzheimer disease 79
AlzGene database 80
ApoE gene 81
ApoE genotype and nitric oxide 82
ApoE genotype modulates AD phenotype 82
APOE genotype and age-related myelin breakdown 83
ApoE receptor interaction with NMDA receptor 83
ApoE and ApoER2 83
ApoE receptor LR11 as regulator of A? 84
Arctic mutation 84
CALHM1 polymorphism and AD 84
CLU, CRI and PICALM 85
CYP46 and risk for AD 85
DAPK1 gene variants and AD 85
Genetic variants associated with late-onset AD 86
LRRTM3 as a candidate gene for AD 86
OGG1 mutations associated with AD 86
SORL1 gene in AD 87
TOMM40 gene and risk of AD 87
Copy number variation (CNV) in LOAD 87
Molecular neuropathology 87
AD as a polygenic disorder 88
Proteomics of AD 88
Introduction 88
Application of proteomic technologies to study AD 88
Protein misfolding in AD 90
Common denominators of AD and prion diseases 91
Amyloid fibrils as a common feature of AD and prion diseases 91
FE65 proteins and AD 92
2. Diagnostic Procedures for Alzheimer Disease 93
Importance of the diagnosis of Alzheimer disease 93
Methods of diagnosis of AD 93
Self-administered olfactory test 94
Neuropsychological testing 94
Assessment and evaluation 95
7-minute screen 95
15-point risk index 96
Measurement of aggregation in anterior segment of the eye 96
Activities of Daily Living 96
Alzheimer Disease Cooperative Study 97
CDR-SOB score 97
Clinician's Interview-Based Impression of Change 97
Resource Utilization in Dementia Battery 97
DETECT? System 97
Electrophysiology 98
EEG-based bispectral index 98
Event-related potentials 98
Early detection of cataract associated with AD 98
Retinal imaging to detect A? deposits 99
Laboratory methods for diagnosis of AD 99
Monitoring of synthesis and clearance rates of A? in the CSF 99
Molecular diagnostics for AD 100
Genetic tests for AD 101
ApoE genotyping 101
Gene expression patterns in AD 101
Molecular fingerprinting of the immune system in AD 102
Microarray-based tests for AD 102
Monoclonal antibody-based in vitro diagnosis of AD from brain tissues 102
Biomarkers of AD 102
The ideal biomarker for AD 104
CSF biomarkers of AD 105
CSF sulfatide as a biomarker for AD 105
Glycerophosphocholine as CSF biomarker in AD 105
Protein biomarkers of AD in CSF 105
Amyloid precursor protein 107
Tau proteins in CSF 107
Tests for the detection of A? in CSF 108
Tests combining CSF tau and A? 108
Urine tests for AD 109
Blood tests for AD 109
Blood A? levels 109
Blood test for AD based on heme oxygenase-1 110
Blood test for AD based on RNA hybridization 110
GSK-3 elevation in white blood cells 111
Lymphocyte Proliferation Test 111
Protein kinase C in red blood cells 111
Tests based on protein biomarkers in blood 111
A skin test for early detection of AD 112
Nanotechnology to measure A?-derived diffusible ligands 112
Simultaneous measurement of several biomarkers for AD 113
Plasma biomarkers of drug response in AD 113
Concluding remarks about biomarkers for AD 114
Imaging in AD 114
Computed tomography 114
Magnetic resonance imaging 114
Arterial spin labeling with MRI 115
Magnetic resonance microscopy 115
Magnetic resonance spectroscopy 116
Single photon emission computed tomography and modifications 116
Positron emission tomography 117
In vivo imaging of A? deposits by PET 119
Pittsburgh compound B and PET 119
18F-AV-45 and PET 120
Florbetaben (BAY 94-9172) and PET 120
In vivo detection of A? plaques by MRI 121
Imaging agents for A? and neurofibrillary tangles 121
Targeting of a chemokine receptor as biomarker for brain imaging 122
Radioiodinated clioquinol as a biomarker for A? 122
Imaging neuroinflammation in AD 123
Preclinical diagnosis of AD 123
Meta-analysis of literature on imaging in AD 124
Alzheimer Disease Neuroimaging Initiative 124
Concluding remarks on imaging for diagnosis of AD 125
Diagnosis of MCI and prediction of AD 125
Diagnosis of MCI 125
Computer-Administered Neurophychological screen for MCI 125
Infrared eye-tracking technology to detect MCI 125
PET for detection of MCI 126
MRI for detection of MCI 126
Presymptomatic detection of AD 126
PredictAD project 127
Use of biomarkers to predict AD in patients with MCI 127
Biochemical biomarkers in CSF for prediction of AD 127
Structural MRI biomarkers for prediction of AD 128
Magnetoencephalography for detection of MCI and AD 128
Concluding remarks about prediction of AD in MCI 129
Ethical aspects of diagnostics for AD 129
Genetic testing for AD 129
Ethical issues of brain imaging in AD 130
Companies involved in diagnosis of AD 131
3. Management of Alzheimer Disease 133
Introduction 133
Cholinergic approaches 133
Mechanism of action of cholinesterase inhibitors 134
Choline and lecithin 135
Donepezil 136
Rivastigmine 137
Galantamine 138
Duration of treatment with ChE inhibitors 139
Comparative studies of ChE inhibitors 139
Donepezil versus rivastigmine 139
Donepezil versus galantamine 140
An assessment and future prospects of anticholinergic therapies 140
Neuroprotection in Alzheimer's disease 141
Memantine 142
Combination of memantine with ChE inhibitors 144
Monoamine oxidase inhibitors 145
Selegiline 145
Synaptoprotection in AD 146
Drugs for noncognitive symptoms in AD 146
Antidepressants 146
Antipsychotics 146
ChE inhibitors for behavioral and psychological disorders in AD 147
Concluding remarks and other drugs for agitation in AD 148
Sensory stimulation 148
Non-pharmacological treatments of AD 148
Management of memory loss in AD 149
Exposure to electromagnetic fields for treatment of AD 149
Application of electrical fields for improvement of cerebral function 149
High-frequency electromagnetic field treatment of AD 150
Vagal nerve stimulation 150
Cerebrospinal fluid shunting 151
Omental transposition 151
Microchip-based hippocampal prosthesis for AD 151
Nutritional therapies for AD 152
Cocktail of dietary supplements for AD 152
Docosahexaenoic acid 152
Magnesium 154
Nicotinamide for the treatment of AD 154
Omega-3 fatty acids 154
Preventing decline of mental function with aging and dementia 155
Prevention of Alzheimer disease 156
Mental training 157
Physical exercise 157
Higher level of conscientiousness and decreased risk of AD 157
Caloric restriction 158
Nutritional factors in prevention of AD 158
Grapes and red wine 158
Black and green teas 159
Caffeine 160
Drugs to prevent Alzheimer disease 160
Preimplantation genetic diagnosis of inherited Alzheimer disease 160
Presymptomatic detection of AD 161
Management of mild cognitive impairment 161
Management of Down syndrome 162
Guidelines for use of anti-dementia drugs in clinical practice 163
General care of the Alzheimer disease patients 164
Strategies for the management of Alzheimer disease 164
4. Research in Alzheimer Disease 165
Introduction 165
Animal models of Alzheimer disease 165
Lesional models 165
Cerebroventricular injection of A? in rats 165
Lentiviral vector-based models of amyloid pathology 166
AAV-mediated gene transfer to increase hippocampal A? 166
Transgenic mouse models 166
Quantitative assessment of amyloid load in transgenic models 168
In vivo magnetic resonance microimaging in transgenic models of AD 168
Transgenic model of AD with suppression of A? production 168
Transgenic AD11 anti-NGF mice 169
Genetically altered mice with deficiency of vesicular ACh transporter 169
Limitations of mouse models of Alzheimer disease 169
Cholesterol-fed rabbits as models for AD 170
Zebrafish model for AD 170
Transgenic invertebrate models of Alzheimer disease 171
Drosophila model of AD 171
Caenorhabditis elegans Alzheimer disease model 172
Cell systems for AD research 172
In vitro neuronal cell Lines 172
Single-gene expression system for use in cell culture 173
Transgenic cells 173
In silico models 174
Estimation of progression rates of Alzheimer disease 174
Clinical trial methods in Alzheimer disease 175
Molecular imaging as a guide to drug development 175
Use of MRI and PET in clinical trials 176
Cognitive-function assessment in clinical trials 176
Clinical trials in mild cognitive impairment 177
Research in AD as a basis for future therapies 177
Use of microarrays for studying pathogenesis of AD 177
Computational brain mapping in AD 177
Study of neurogenesis in AD 178
Study of 3D structure of A? 178
Solid-state NMR to study precursors of A? 178
Research in Alzheimer disease at academic centers 178
Role of NIH in AD research 179
NIH Clinical Trials Database for AD 179
Alzheimer Research Consortium 179
The National Institute on Aging and AD research 179
5. Drug Discovery & Development for Alzheimer Disease 181
Introduction 181
Categories of drugs in development for AD 181
Memory-enhancing drugs 183
Enhancing memory by drugs that block eIF2? phosphorylation 183
Drugs based on cholinergic approaches 183
AP2238 184
Butyrylcholinesterase inhibitors 184
Donepezil-tacrine hybrids 184
Drugs modulating gamma-aminobutyric acid receptors 185
Ganstigmina 185
Methanesulfonyl fluoride 185
Muscarinic receptor modulators 186
Muscarinic M1 agonists 186
Muscarinic M2 antagonists 187
Nicotine and nicotinic receptor modulators 187
Nicotine 187
Nicotinic receptor modulators 188
GTS21 189
Ispronicline 189
JWB1-84-1 190
Neuropeptide/neurotransmitters 190
Somatostatin release enhancers 190
Glutamate receptor modulators 190
Physiology and pharmacology of glutamate receptors 191
NMDA receptor ion channel complex 191
Metabotropic glutamate receptors 192
Glutamate receptor modulators as potential therapeutics for AD 193
Non-competitive NMDA modulators 194
AMPA modulators 194
Drugs affecting multiple neurotransmitters 195
Ensaculin 195
NS2330 195
RS-1259 195
Lecozotan 196
Vaccines for AD 196
Active immunization with A? 196
AN-1792 vaccine 196
Complications in clinical trials with AN-1792 197
Effects of A? vaccine on the brain 197
Strategies to avoid undesirable effect of A? vaccination 198
Passive immunization in AD with monoclonal antibodies 199
Delivery of the passive antibody directly to the brain 201
Systemic injection of MAbs to treat AD 201
Combination of A? immunotherapy and CD40-CD40L blockade 202
Shaping the immune responses elicited against A? 202
Gene vaccination 202
Modified A? nasal vaccine 203
Transdermal A? vaccination 203
Other vaccines for AD 203
Nasal vaccination with Proteosome? adjuvant 204
T-cell vaccination with glatiramer acetate adjuvant 204
Early start of immunotherapy to clear A? plaques 204
Reversal of cholinergic dysfunction by anti-A? antibody 205
Immune modulation via TRL9 to reduce A? 205
Mechanisms by which A? antibodies reduce amyloid accumulation in the brain 205
Perspectives on vaccines for AD 206
Companies involved in AD vaccines 208
Inhibition of amyloid precursor protein aggregation 208
Secretase inhibitors 208
Neuroprotection by ?-secretase cleaved APP 209
-secretase inhibitors 209
-secretase inhibitors 210
Substrate-targeting by ?-secretase modulators 211
Amyloid-derived diffusible ligands 211
GABA receptor modulation by etazolate and APP processing 211
Depletion of serum amyloid P 212
Trojan-horse approach to prevent build-up of A? aggregates 212
Drugs that inhibit the formation of A? 213
22R-hydroxycholesterol 213
Acylaminopyrazole 213
Chelation therapy for AD 214
Clioquinol and PBT2 214
Copper chelation by FKBP52 215
Zinc chelation from amyloid plaques 215
Next generation multifunctional chelating agents for AD 216
Tetrahydrocannabinol 216
NSAIDs 217
Flurbiprofen analogs with A?42-lowering action 218
Nitric oxide-donating NSAIDs 218
In vivo demonstration of the effects of NSAIDs on brain in AD 219
Imatinib mesylate 219
Laminin 219
Paclitaxel 220
Phenserine 220
Tolserine 221
Platinum-based inhibitors of A? 221
Heparin and its derivatives 221
A reassessment of the role of heparin in AD 221
Enoxaparin 222
Heparan sulfate 222
Scyllo-cyclohexanehexol 222
Ubiquitin C-terminal hydrolase L1 222
Drugs to prevent the formation of NFTs 223
Tau suppression 223
ApoE4 as a therapeutic target in AD 224
Strategies to enhance clearance of A? 224
Removal of A? deposits by nanotechnology 225
Enhanced PKC? activity promotes clearance of A? 225
Role of matrix metalloproteinases in clearance of A? 226
Small molecule DAPH for clearance of amyloid 226
Clearance of A? across the blood-brain barrier 226
Therapeutics to reverse cerebral A? deposits 227
4,5-dianilinophthalimide for disruption of A?1-42 fibrils 227
ABCA1 overexpression to lower amyloid deposits 227
-sheet breakers 228
Blocking ApoE/A? interaction to reduce A? plaques 228
Inhibitors of A? dehydrogenase 228
Intravenous immune globulin 229
Meptides 230
SAN-61 for cleavage of fibril and soluble amyloid 230
Serum amyloid P component depletion 231
Companies developing A?-directed therapeutics for AD 231
Antiinflammatory and antimicrobial drugs 232
Dapsone 232
Antimicrobial drugs against C. pneumoniae 233
PPAR-gamma agonists 233
Inhibitors of neuroinflammation 234
Cyclophosphamide 234
Etanercept 234
MW01-5-188WH 235
VP015 235
Antidiabetic drugs 235
Rosiglitazone 236
Pioglitazone 236
Nootropics 236
Acetyl-L-carnitine 237
Cerebrolysin 237
Ergot derivatives 237
Lisuride 238
Dihydroergocryptine 238
Neuroprotective effect drugs not primarily developed for AD 238
Antihypertensive drugs 239
Angiotensin-converting enzyme inhibitors 239
Angiotensin receptor blockers 239
Dimebolin 240
Drugs acting on estrogen receptors 240
Estrogen 241
Raloxifene 241
Neurosteroids 242
Pregnenolone sulfate 242
Dehydroepiandrosterone 242
Lithium 243
MAO-B inhibitors 243
Ladostigil tartrate 243
Memoquin 244
Methylene blue 244
Nimodipine 245
Rapamycin 245
Testosterone 245
Valproic acid 246
Future prospects of neuroprotection in AD 247
Targeting Cdk5 pathway 247
Antioxidants 248
Colostrinin 248
Curcumin 248
Melatonin 249
Synthetic catalytic scavengers 249
Dehydroascorbic acid 250
Omega-3 fatty acids 250
Vitamins 250
Vitamin E as antioxidant 251
Vitamins to lower homocysteine 251
Folic acid 251
Aminopyridazines 251
Nanobody-based drugs for AD 252
Nitric oxide based therapeutics for AD 252
Nitric oxide mimetics 252
iNOS inhibitors for AD 253
Novel drugs for AD from natural resources 253
Berberine chloride 254
Centella asiatica 254
Ginko biloba 255
Huperzine-A 256
Hyperforin 256
Melissa officinalis 256
Nostocarboline derived from cyanobacteria 257
PTI-00703 257
Salvia 257
Securinega suffruticosa 257
Withania somnifera 258
ZT-1 258
Cholesterol and AD 258
Role of statins in reducing the risk of Alzheimer disease 259
Neuroprotective effect of statins unrelated to cholesterol lowering 260
ACAT inhibitors 260
Role of gene for cholesterol ester transfer protein 261
Cholesterol 24S-hydroxylase as a drug target for AD 261
Selectively increase of ApoA-I production 261
Neurotrophic factors 262
Activity-dependent neuroprotective protein 262
Brain derived neurotrophic factor 262
Insulin-like growth factor-1 262
Nerve growth factor 263
Neotrofin (AIT-082) 264
Limitations of the use of NTFs for AD 264
Role of serotonin modulators in AD 265
Xaliproden 265
5-HT1A receptor antagonists 265
5-HT6 antagonists 265
5-HT4 receptor agonists 266
PRX-03140 266
Cell therapy for AD 266
Stem cell transplantation for AD 267
Potential benefits of grafting NSCs in AD 267
NSCs improve cognition in AD via BDNF 267
Drugs for enhancing neuronal differentiation of implanted NSCs 268
Implantation of encapsulated cells for delivering NGF 268
Gene therapy for AD 268
ApoE gene therapy 268
Humanin gene therapy 268
Neprilysin gene therapy 269
NGF gene therapy 269
Targeting plasminogen activator inhibitor type-1 gene 270
Antisense approaches to AD 270
RNAi approaches to AD 271
Combined therapeutic approaches to AD 272
Drug delivery for Alzheimer disease 272
Delivery of thyrotropin-releasing hormone analogs by molecular packaging 273
Nanoparticle-based drug delivery for Alzheimer's disease 273
Transdermal drug delivery in Alzheimer's disease 274
Transdermal rivastigmine 274
Intranasal delivery of therapeutics for AD 274
Intranasal delivery of tacrine 274
Intranasal delivery of nerve growth factor to the brain 275
Circadian rhythms and timing of cholinesterase inhibitor therapy 275
Clinical trials for AD 275
Drugs for AD that were discontinued in clinical trials 280
Evaluation of clinical trials of AD 282
Monitoring of cognitive function during clinical trials 282
Drug discovery for AD 282
Drugs acting on signaling pathways 282
Activation of GTPase signaling by Cytotoxic Necrotizing Factor 1 282
Drugs to reverse inhibition of the PKA/CREB pathway in AD 283
Inhibition of the CD40 signaling pathway 283
JNK pathway as a target 284
Mitogen-activated protein kinase pathway as target 284
Protein kinase C activators 285
Electrophysiological detection of drug target for neuroprotection in early AD 285
Genomics-based drug discovery 285
High through screening for AD drug candidates 285
Proteomics and drug discovery for AD 286
Small molecule compounds binding to neurotrophin receptor p75NTR 287
Targeting Vav in tyrosine kinase signaling pathway 288
Novels targets/receptors for AD drug discovery 288
Activation of cerebral Rho GTPases 288
Activators of insulin-degrading enzyme 288
Blockade of TGF-?-Smad2/3 signaling in peripheral macrophages 289
Blockers of A? calcium channel 289
Casein kinase 1 289
Cyclin-dependent kinase-5 290
Heat shock protein 90 inhibitors 290
Histone deacetylase 1 290
Inactivation of aph-1 and pen-2 reduces APP cleavage 291
NF-?B inhibitors 291
Kinases and phosphatases as targets for AD therapeutics 291
Phosphodiesterase inhibitors 292
Pin 1 as a target in AD 292
Protein phosphatase 5 as a neuroprotective in AD 293
Src homology-containing protein-1 inhibitors 293
Targeting GABAergic system 293
Pharmacogenomics of Alzheimer disease 294
Personalized therapy of AD 294
Genotyping and AD therapeutics 294
Biomarkers of AD/companion diagnostics for cholinesterase inhibitors 295
Regulatory aspects of drug development for AD 296
EMEA guidelines for drug development for AD 296
Concluding remarks and future prospects of drugs for AD 296
6. Markets & Finances of AD Care 299
Introduction 299
Pharmacoeconomics of treatment of AD 299
Quality of Life in relation to economics of AD 299
Costs associated with Alzheimer disease 299
Pharmacoeconomics of donepezil 300
Pharmacoeconomics studies using rivastigmine 300
Pharmacoenonomics studies using galantamine 301
A comparison of pharmacoenonomics outcomes with different ChE inhibitors 301
Pharmacoenonomics studies using memantine 302
Patterns of AD care in major markets 302
Care of AD patients in the US 302
Cost of care 302
Medicare and AD 303
Patterns of practice in AD care 304
Opinions of physicians' organizations on drugs for dementia 304
Care of AD patients in the UK 305
Cost of care 305
Patterns of practice in AD care 305
Retraction of NICE recommendations to NHS 306
Care of AD patients in Germany 307
Care of AD patients in France 307
Care of AD patients in Italy 308
Care of AD patients in Spain 308
Care of AD patients in Japan 308
Markets for AD diagnostics 309
Markets for AD therapeutics 309
Geographical markets for AD 309
Markets for currently approved drugs for AD 310
Markets for generic AD drugs 310
Future growth of AD market 311
Statins 311
Limitations of AD drug development by the biotechnology industry 311
Unmet needs in the management of AD 312
Drivers of AD markets 313
Increase of the aged populations 314
Increase in the number of approved drugs for AD 314
Limitations of the current therapies 314
Improvements in diagnosis 314
Increasing awareness of the disease 315
7. Companies 317
Introduction 317
Profiles of companies 317
Collaborations 462
8. References 467
Tables
Table 1 1: Historical landmarks relevant to Alzheimer disease 19
Table 1 2: Clinical features of Alzheimer disease 20
Table 1 3: Non-Alzheimer dementias 24
Table 1 4: NINCDS-ADRDA Criteria for diagnosis of Alzheimer disease 29
Table 1 5: Relation of mutations in amyloid precursor protein to CNS disorders 36
Table 1 6: Risk factors for Alzheimer's disease 64
Table 1 7: Genes linked to AD 79
Table 1 8: Abnormalities of expression of brain proteins in Down's syndrome and AD 89
Table 2 1: Classification of methods of diagnosis of Alzheimer disease 93
Table 2 2: Neuropsychological test batteries and scales for Alzheimer's disease 94
Table 2 3: Available molecular diagnostic tests for Alzheimer disease 100
Table 2 4: Classification of biomarkers of AD in blood and CSF 103
Table 2 5: Characteristics of an ideal biomarker for Alzheimer disease 104
Table 2 6: Companies involved in the diagnosis of Alzheimer disease 131
Table 3 1: Classification of treatments for Alzheimer disease 133
Table 3 2: Cholinergic approaches used in the treatment of Alzheimer disease 134
Table 3 3: Categories of neuroprotective agents for Alzheimer disease 141
Table 3 4: Strategies for prevention of Alzheimer disease 156
Table 3 5: Guidelines for the treatment of dementia 163
Table 4 1: Transgenic mouse models of Alzheimer disease 166
Table 5 1: Classification of therapies in development for Alzheimer disease 181
Table 5 2: Drugs for AD targeting nACh receptors 188
Table 5 3: Ionotropic glutamate receptors 191
Table 5 4: Classification of mGluRs 191
Table 5 5: Glutamate receptor modulators as potential therapeutic agents in AD 193
Table 5 6: Companies involved in developing vaccines for AD 208
Table 5 7: Companies developing A?-directed therapeutics for AD 231
Table 5 8: Innovative neuroprotective approaches for Alzheimer disease 238
Table 5 9: Herbal therapies for AD 253
Table 5 10: Novel drug delivery methods for Alzheimer disease therapies 272
Table 5 11: Clinical trials in Alzheimer disease 275
Table 5 12: Discontinued, failed or inconclusive clinical trials of Alzheimer disease 280
Table 6 1: Direct and indirect costs associated with Alzheimer disease 300
Table 6 2: Prevalence of AD in major markets 2009-2019 309
Table 6 3: AD market values from 2009-2019 in the seven major world markets 310
Table 6 4: Markets for currently approved AD drugs 2009-2019 310
Table 6 5: Potential markets for drugs in development 2009-2019 311
Table 6 6: Limitations of AD drug discovery and development by the biotechnology industry 312
Table 6 7: Factors that drive AD markets 313
Table 7 1: Major players in Alzheimer's disease therapeutics 317
Table 7 2: Collaborations relevant to Alzheimer disease 462
Figures
Figure 1 1: Percentages of world population of people over the age of 65 according to more developed and less developed portions ? 2000 to 2050. 30
Figure 1 2: Prevalence of different types of dementia 31
Figure 1 3: Mechanisms of A? clearance 43
Figure 1 4: Nitric oxide neurotoxicity and neuroprotection in relation to Alzheimer disease 58
Figure 1 5: Oxidative stress and Alzheimer disease 60
Figure 1 6: Role of proteosome inhibition in A? generation and neurodegeneration 64
Figure 1 7: Pathomechanism of AD 76
Figure 3 1: Metabolism of acetylcholine 135
Figure 3 2: Neuroprotective effective of galantamine in AD 139
Figure 3 3: Strategies for the management of Alzheimer disease 164
Figure 5 1: NMDA receptor ion channel complex. 192
Figure 5 2: Neurotoxicity due to misfolding of A?1-42 227
Figure 5 3: Role of proteomics in drug discovery and development for Alzheimer disease 286
Figure 6 1: Unmet needs in the management of Alzheimer disease 313
To order this report:
Drug and Medication Industry: Alzheimer disease - new drugs, markets and companies
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Nicolas Bombourg Reportlinker Email: [email protected] US: (805) 652-2626 Intl: +1 805-652-2626 |
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