PL EN


Preferences help
enabled [disable] Abstract
Number of results
2008 | 8 | 2 | 77-83
Article title

Strategie aktywnej i pasywnej immunizacji jako terapii choroby alzheimera

Authors
Content
Title variants
EN
Active and passive immunization strategies as treatments of Alzheimer’s disease
Languages of publication
EN PL
Abstracts
EN
currently available pharmacotherapeutics (cholinesterase inhibitors and memantin) for Alzheimer’s disease (AD) exert mainly symptomatic effect and doubtful, if any, disease-modifying activities. Strategies of active and passive immunization were very successful in the last 10 years, mainly, however, with the use of experimental animal models of the disease. More recently, several human trials have been undertaken with mixed results obtained. Some support was found for the idea that immunotherapy may influence natural disease history, at least at the level of neuropathology and biomarkers and, to the less extend, neuroimaging findings and cognition. The paper presents recent developments in the use of immunotherapy of AD both with animal pasywmodels as well as human clinical trials. An attempt is also made to elucidate possible mechanisms of action of this novel treatment approach. Particularly, the difficulties in translating results obtained in animal studies into clinical trials in humans has been underlined and discussed. The results of the very first human trial with the use of AN-1792 vaccination are critically discussed with special reference to the possible mechanisms of the observed severe complications of this treatment modality (brain inflammation). currently, several other studies with active immunization are on the way, in which novel technologies diminishing the risk of brain inflammation were used. Finally, article presents several clinical trials with the use of passive immunization strategies, showing the advantages of this approach, particularly in the context of tolerability.
PL
Obecnie dostępne metody leczenia choroby Alzheimera (inhibitory cholinesterazy i memantyna) mają prawdopodobnie głównie działanie objawowe, a ich wpływ na naturalny przebieg choroby jest wątpliwy. Strategie aktywnej i pasywnej immunizacji są intensywnie badane przez ostatnie 10 lat. Wyniki badań eksperymentalnych oraz wstępne wyniki badań chorych z AD wskazują, że działanie immunoterapii może wykraczać poza efekt objawowy i wpływać nie tylko na objawy (poznawcze, behawioralne), ale także na progresję neuropatologiczną i, prawdopodobnie, biomarkery. W pracy przedstawiono wyniki badań z wykorzystaniem modeli zwierzęcych AD i użyciem metod aktywnej i pasywnej immunizacji anty-Ab. Omówiono trudności z przełożeniem wyników uzyskanych z wykorzystaniem zwierząt laboratoryjnych na potencjalne metody terapeutyczne u ludzi. Opisano ponadto pierwsze wyniki badań na ludziach i podjęto próbę odpowiedzi na pytanie o mechanizmy działania immunoterapii w AD. Krytycznej analizie poddano wyniki pierwszych badań klinicznych na ludziach z użyciem szczepionki AN-1792, ze szczególnym uwzględnieniem możliwych przyczyn obserwowanych w tych badaniach powikłań (zapalenie mózgu). Obecnie prowadzonych jest kilka innych badań z aktywną immunizacją, w których zastosowano technologie zmniejszające ryzyko zapalenia mózgu. W pracy omówiono także prowadzone obecnie próby kliniczne z wykorzystaniem technik pasywnej immunizacji i wskazano na potencjalne przewagi tej metody nad immunizacją aktywną, zwłaszcza w kontekście tolerancji leczenia.
Discipline
Year
Volume
8
Issue
2
Pages
77-83
Physical description
References
  • 1. Games D., Adams D., Alessandrini R. i wsp.: Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature 1995; 373: 523-527.
  • 2. Johnson-Wood K., Lee M., Motter R. i wsp.: Amyloid precursor protein processing and Ab42 deposition in a transgenic mouse model of Alzheimer disease. Proc. Natl Acad. Sci. USA 1997; 94: 1550-1555.
  • 3. Schenk D., Barbour R., Dunn W. i wsp.: Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999; 400: 173-177.
  • 4. Weiner H.L., Lemere C.A., Maron R. i wsp.: Nasal administration of amyloid-β peptide decreases cerebral amyloid burden in a mouse model of Alzheimer’s disease. Ann. Neurol. 2000; 48: 567-579.
  • 5. Bard F., Barbour R., Cannon C. i wsp.: Epitope and isotype specificities of antibodies to β-amyloid peptide for protection against Alzheimer’s disease-like neuropathology. Proc. Natl Acad. Sci. USA 2003; 100: 2023-2028.
  • 6. Janus C., Pearson J., McLaurin J. i wsp.: Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer’s disease. Nature 2000; 408: 979-982.
  • 7. Morgan D., Diamond D.M., Gottschall P.E. i wsp.: Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer’s disease. Nature 2000; 408: 982-985.
  • 8. Das P., Murphy M.P., Younkin L.H. i wsp.: Reduced effectiveness of Aβ1-42 immunization in APP transgenic mice with significant amyloid deposition. Neurobiol. Aging 2001; 22: 721-727.
  • 9. Austin L., Arendash G.W., Gordon M.N. i wsp.: Shortterm β-amyloid vaccinations do not improve cognitive performance in cognitively impaired APP + PS1 mice. Behav. Neurosci. 2003; 117: 478-484.
  • 10. Oddo S., Vasilevko V, Caccamo A. i wsp.: Reduction of soluble Aβ and tau, but not soluble Aβ alone, ameliorates cognitive decline in transgenic mice with plaques and tangles. J. Biol. Chem. 2006; 281: 39413-39423.
  • 11. Oddo S., Caccamo A., Shepherd J.D. i wsp.: Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron 2003; 39: 409-421.
  • 12. Bard F, Cannon C., Barbour R. i wsp.: Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat. Med. 2000; 6: 916-919.
  • 13. DeMattos R.B., Bales K.R., Cummins D.J. i wsp.: Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer’s disease. Proc. Natl Acad. Sci. USA 2001; 98: 8850-8855.
  • 14. Kotilinek L.A., Bacskai B., Westerman M. i wsp.: Reversible memory loss in a mouse transgenic model of Alzheimer’s disease. J. Neurosci. 2002; 22: 6331-6335.
  • 15. Wilcock D.M., Rojiani A., Rosenthal A. i wsp.: Passive immunotherapy against Aβ in aged APP-transgenic mice reverses cognitive deficits and depletes parenchymal amyloid deposits in spite of increased vascular amyloid and microhemorrhage. J. Neuroinflammation 2004; 1: 24.
  • 16. Oddo S., Billings L., Kesslak J.P i wsp.: Aβ immunotherapy leads to clearance of early, but not late, hyperphos-phorylated tau aggregates via the proteasome. Neuron 2004; 43: 321-332.
  • 17. Hutton M., McGowan E.: Clearing tau pathology with Aβ immunotherapy - reversible and irreversible stages revealed. Neuron 2004; 43: 293-294.
  • 18. Pfeifer M., Boncristiano S., Bondolfi L. i wsp.: Cerebral hemorrhage after passive anti-Aβ immunotherapy. Science 2002; 298: 1379.
  • 19. Racke M.M., Boone L.I., Hepburn D.L. i wsp.: 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 β. J. Neurosci. 2005; 25: 629-636.
  • 20. Ferrer I., Boada Rovira M., Sanchez Guerra M.L. i wsp.: Neuropathology and pathogenesis of encephalitis following amyloid-beta immunization in Alzheimer’s disease. Brain Pathol. 2004; 14: 11-20.
  • 21. Schenk D.: Amyloid-β immunotherapy for Alzheimer’s disease: the end of the beginning. Nat. Rev. Neurosci. 2002; 3: 824-828.
  • 22. Bayer A.J., Bullock R., Jones R.W i wsp.: Evaluation of the safety and immunogenicity of synthetic Aβ42 (AN 1792) in patients with AD. Neurology 2005; 64: 94-101.
  • 23. Senior K.: Dosing in phase II trial of Alzheimer’s vaccine suspended. Lancet Neurol. 2002; 1: 3.
  • 24. Orgogozo J.M., Gilman S., Dartigues J.F. i wsp.: Subacute meningoencephalitis in a subset of patients with AD after Ap42 immunization. Neurology 2003; 61: 46-54.
  • 25. Nicoll J.A., Wilkinson D., Holmes c. i wsp.: Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report. Nat. Med. 2003; 9: 448-452.
  • 26. Masliah E., Hansen L., Adame A. i wsp.: A vaccination effects on plaque pathology in the absence of encephalitis in Alzheimer disease. Neurology 2005; 64: 129-131.
  • 27. Fox N.c., Black R.S., Gilman S. i wsp.; AN1792(QS-21)-201 Study: effects of Ab immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology 2005; 64: 1563-1572.
  • 28. Gilman S., Koller M., Black R.S. i wsp.; AN1792(QS-21)-201 Study Team: clinical effects of Ab immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005; 64: 1553-1562.
  • 29. Hock c., Konietzko u., Streffer J.R. i wsp.: Antibodies against β-amyloid slow cognitive decline in Alzheimer’s disease. Neuron 2003; 38: 547-554.
  • 30. Winblad B.: Safety, tolerability and immunogenicity of the Ab immunotherapeutic vaccine CAD106 in a first-in-man study in Alzheimer patients. Alzheimer’s & Dementia. Abstracts of the 11th ICAD Conference, Chicago 2008; S2-04-06.
  • 31. Gilman S.: Clinical trials of bapineuzumab a beta-amyloid-targeted immunotherapy in patients with mild-to-mod-erate Alzheimers disease. Alzheimer’s & Dementia. Abstracts of the 11th ICAD Conference, Chicago 2008; 03-04-05.
  • 32. Dodel R.C., Du Y., Depboylu C. i wsp.: Intravenous immunoglobulins containing antibodies against β-amyl-oid for the treatment of Alzheimer’s disease. J. Neurol. Neurosurg. Psychiatry 2004; 75: 1472-1474.
  • 33. Relkin N.R., Szabo P., Adamiak B. i wsp.: 18-month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol. Aging w druku 2008.
  • 34. Bacskai B.J., Kajdasz S.T, Christie R.H. i wsp.: Imaging of amyloid-β deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy. Nat. Med. 2001; 7: 369-372.
  • 35. Solomon B., Koppel R., Hanan E., Katzav T: Monoclonal antibodies inhibit in vitro fibrillar aggregation of the Alzheimer β-amyloid peptide. Proc. Natl Acad. Sci. USA 1996; 93: 452-455.
  • 36. Solomon B., Koppel R., Frankel D., Hanan-Aharon E.: Disaggregation of Alzheimer β-amyloid by site-directed mAb. Proc. Natl Acad. Sci. USA 1997; 94: 4109-4112.
  • 37. Frenkel D., Solomon B., Benhar I.: Modulation of Alzheimer’s β-amyloid neurotoxicity by site-directed single-chain antibody. J. Neuroimmunol. 2000; 106: 23-31.
  • 38. Das P., Howard V, Loosbrock N. i wsp.: Amyloid-β immunization effectively reduces amyloid deposition in FcRg-/- knock-out mice. J. Neurosci. 2003; 23: 8532-8538.
  • 39. Bacskai B.J., Kajdasz S.T, McLellan M.E. i wsp.: Non-Fc-mediated mechanisms are involved in clearance of amyl-oid-β in vivo by immunotherapy. J. Neurosci. 2002; 22: 7873-7878.
  • 40. Fiala M., Cribbs D.H., Rosenthal M., Bernard G.: Phagocytosis of amyloid-β and inflammation: two faces of innate immunity in Alzheimer’s disease. J Alzheimers Dis. 2007; 11: 457-463.
  • 41. Mor F., Monsonego A.: Immunization therapy in Alzheimer’s disease. Expert Rev. Neurother. 2006; 6: 653-659.
  • 42. Rosenmann H., Grigoriadis N., Karussis D. i wsp.: Tauo-pathy-like abnormalities and neurologic deficits in mice immunized with neuronal tau protein. Arch. Neurol. 2006; 63: 1459-1467.
  • 43. Rakover I., Arbel M., Solomon B.: Immunotherapy against APP β-secretase cleavage site improves cognitive function and reduces neuroinflammation in Tg2576 mice without a significant effect on brain Aβ levels. Neurodegener. Dis. 2007; 4: 392-402.
  • 44. Masliah E., Rockenstein E., Adame A. i wsp.: Effects of α-synuclein immunization in a mouse model of Parkinson’s disease. Neuron 2005; 46: 857-868.
  • 45. Urushitani M., Ezzi S.A., Julien J.P.: Therapeutic effects of immunization with mutant superoxide dismutase in mice models of amyotrophic lateral sclerosis. Proc. Natl Acad. Sci. USA 2007; 104: 2495-2500.
  • 46. Heppner F.L., Musahl C., Arrighi I. i wsp.: Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies. Science 2001; 294: 178-182.
  • 47. Sigurdsson E.M., Sy M.S., Li R. i wsp.: Anti-prion antibodies for prophylaxis following prion exposure in mice. Neurosci. Lett. 2003; 336: 185-187.
  • 48. Bombois S., Maurage C.A., Gompel M. i wsp.: Absence of β-amyloid deposits after immunization in Alzheimer disease with Lewy body dementia. Arch. Neurol. 2007; 64: 583-587.
Document Type
article
Publication order reference
YADDA identifier
bwmeta1.element.psjd-17ee0bb4-8ec3-467f-aa5c-470d2eed4ac0
Identifiers
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.