Clinical immunotherapy trials in Alzheimer's disease

Drug Discovery Today: Therapeutic Strategies

Volumn 5, Issue 3, 2008, Pages 177-183

  Hawkes, Cheryl A ^a   McLaurin, JoAnne ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

AAC 001; AD 01; ALZHEIMER DISEASE VACCINE; AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN ANTIBODY; BAPINEUZUMAB; CAD 106; DIPHTHERIA TOXOID CRM197; GSK 933776A; IMMUNOGLOBULIN; LY 2062430; PF 04360365; PLACEBO; POLYSORBATE 80; QS 21; R 1450; UNCLASSIFIED DRUG; V 950;

ABSENCE OF SIDE EFFECTS; ACCIDENTAL INJURY; ALZHEIMER DISEASE; ANXIETY; AORTA STENOSIS; BACKACHE; CHILL; CLINICAL TRIAL; COGNITIVE DEFECT; CONFUSION; DISEASE MODEL; DISEASE SEVERITY; DOSAGE SCHEDULE COMPARISON; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG TARGETING; EDEMA; GAIT DISORDER; HEADACHE; HUMAN; HYPERTENSION; IMMUNOTHERAPY; INFECTION; MENINGOENCEPHALITIS; MUSCLE SPASM; NONHUMAN; PARANOIA; REVIEW; SIDE EFFECT; SKIN INJURY; THORAX PAIN; TREATMENT OUTCOME; VASCULITIS; VOMITING; WEIGHT REDUCTION;

EID: 61849158868     PISSN: 17406773     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ddstr.2008.09.004     Document Type: Review

References (36)

1. Schenk D., et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400 (1999) 173-177
2. Hawkes C.A., and McLaurin J. Immunotherapy as treatment for Alzheimer's disease. Expert Rev. Neurother. 7 (2007) 1535-1548
3. Bayer A.J., et al. Evaluation of the safety and immunogenicity of synthetic Abeta42 (AN1792) in patients with AD. Neurology 64 (2005) 94-101
4. Schenk D. Amyloid-beta immunotherapy for Alzheimer's disease: the end of the beginning. Nat. Rev. Neurosci. 3 (2002) 824-828
5. Senior K. Dosing in phase II trial of Alzheimer's vaccine suspended. Lancet Neurol. 1 (2002) 3
6. Orgogozo J.M., et al. Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 61 (2003) 46-54
7. Nicoll J.A., et al. Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat. Med. 9 (2003) 448-452
8. Ferrer I., et al. Neuropathology and pathogenesis of encephalitis following amyloid-beta immunization in Alzheimer's disease. Brain Pathol. 14 (2004) 11-20
9. Masliah E., et al. Abeta vaccination effects on plaque pathology in the absence of encephalitis in Alzheimer disease. Neurology 64 (2005) 129-131
10. Bombois S., et al. Absence of beta-amyloid deposits after immunization in Alzheimer disease with Lewy body dementia. Arch. Neurol. 64 (2007) 583-587
11. Holmes C., et al. Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 372 (2008) 216-223
12. Gilman S., et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology 64 (2005) 1553-1562
13. Hock C., et al. Generation of antibodies specific for beta-amyloid by vaccination of patients with Alzheimer disease. Nat. Med. 8 (2002) 1270-1275
14. Hock C., et al. Antibodies against beta-amyloid slow cognitive decline in Alzheimer's disease. Neuron 38 (2003) 547-554
15. Fox N.C., et al. Effects of Abeta immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology 64 (2005) 1563-1572
16. McLaurin J., et al. Therapeutically effective antibodies against amyloid-beta peptide target amyloid-beta residues 4-10 and inhibit cytotoxicity and fibrillogenesis. Nat. Med. 8 (2002) 1263-1269
17. Cribbs D.H., et al. Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with beta-amyloid. Int. Immunol. 15 (2003) 505-514
18. Winblad B. Safety, tolerability and immunogenicity of the aβ immunotherapeutic vaccine Cad106 in a first-in-man study in Alzheimer patients. International Conference on Alzheimer's Disease 2008. Chicago, IL, USA, July 26-31, 2008 (2008) (Abstract S2-04-06)
19. Wilcock D.M., et al. Intracranially administered anti-Abeta antibodies reduce beta-amyloid deposition by mechanisms both independent of and associated with microglial activation. J. Neurosci. 23 (2003) 3745-3751
20. Wilcock D.M., et al. Passive amyloid immunotherapy clears amyloid and transiently activates microglia in a transgenic mouse model of amyloid deposition. J. Neurosci. 24 (2004) 6144-6151
21. Bussiere T., et al. Morphological characterization of Thioflavin-S-positive amyloid plaques in transgenic Alzheimer mice and effect of passive Abeta immunotherapy on their clearance. Am. J. Pathol. 165 (2004) 987-995
22. Buttini M., et al. Beta-amyloid immunotherapy prevents synaptic degeneration in a mouse model of Alzheimer's disease. J. Neurosci. 25 (2005) 9096-9101
23. Schroeter S., et al. Immunotherapy reduces vascular amyloid-beta in PDAPP mice. J. Neurosci. 28 (2008) 6787-6793
24. Grundman M., and Black R. Clinical trials of bapineuzumab a beta-amyloid-targeted immunotherapy in patients with mild-to-moderate Alzheimers disease. International Conference on Alzheimer's Disease 2008. Chicago, IL, USA, July 26-31, 2008 (2008) (Abstract O3-04-05)
25. Dodel R.C., et al. Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 75 (2004) 1472-1474
26. Relkin N.R., et al. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol. Aging (2008) 10.1016/j.neurobiolaging.2007.12.021 [Epub ahead of print]
27. Tsakanikas D., et al. Effects of uninterrupted intravenous immunoglobulin treatment of Alzheimer's disease for 9 months. International Conference on Alzheimer's Disease 2008. Chicago, IL, USA July 26-31, 2008 (2008) (Abstract P4-351)
28. Siemers E.R. Safety, tolerability and biomarker effects of an Abeta monoclonal antibody administered to patients with Alzheimer's disease. International Conference on Alzheimer's Disease 2008. Chicago, IL, USA, July 26-31, 2008 (2008) (Abstract P4-346)
29. Pfeifer M., et al. Cerebral hemorrhage after passive anti-Abeta immunotherapy. Science 298 (2002) 1379
30. Racke M.M., et al. Exacerbation of cerebral amyloid angiopathy-associated microhemorrhage in amyloid precursor protein transgenic mice by immunotherapy is dependent on antibody recognition of deposited forms of amyloid beta. J. Neurosci. 25 (2005) 629-636
31. Wilcock D.M., et al. Passive immunotherapy against Abeta in aged APP-transgenic mice reverses cognitive deficits and depletes parenchymal amyloid deposits in spite of increased vascular amyloid and microhemorrhage. J. Neuroinflam. 1 (2004) 24
32. Wilcock D.M., et al. Amyloid-beta vaccination, but not nitro-nonsteroidal anti-inflammatory drug treatment, increases vascular amyloid and microhemorrhage while both reduce parenchymal amyloid. Neuroscience 144 (2007) 950-960
33. St George-Hyslop P.H., and Morris J.C. Will anti-amyloid therapies work for Alzheimer's disease?. Lancet 372 (2008) 180-182
34. Vellas B., et al. Endpoints for trials in Alzheimer's disease: a European task force consensus. Lancet Neurol. 7 (2008) 436-450
35. Morris J.C., et al. Mild cognitive impairment represents early-stage Alzheimer disease. Arch. Neurol. 58 (2001) 397-405
36. Gomez-Isla T., et al. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J. Neurosci. 16 (1996) 4491-4500