Name:	AN1792
Other Names:	AIP 001
Therapeutic Applications:	Mild to moderate Alzheimer Disease
Therapy Types:	Protein: active immunization, peptide vaccine
Mechanisms:	Active immunotherapy
Development Status:	investigational in U.S.
FDA Phase:	Discontinued
Primary Medical Role:	Vaccination with Aβ1-42 peptide is a potential treatment and prevention for Alzheimer's disease in facilitating clearance of amyloid plaques. AN1792 is a synthetic Aβ1-42 peptide conjugated to a surface-active saponin adjuvant QS-21.
Role in Alzheimer's Disease:	AN1792 is a synthetic form of the 42 amino acid beta amyloid peptide. Extensive preclinical evidence shows that immunization with Aβ1-42 peptide can prevent or reverse the development of the neuropathological hallmarks of Alzheimer's diseases, including extensive amyloid plaque formation, neuritic dystrophy, synaptic loss and gliosis (Schenk et al 1999). The history of AN1792 has been extensively chronicled in Alzforum News: See Vaccinating Against Plaques and Live Discussion: Alzheimer Immunotherapy Trial Grounded Phase II clinical trial NCT00021723 was initiated in 2001 and abruptly terminated in January 2002 due to the development of aseptic meningoencephalitis and leukoencephalopathy in 6% Aβ1-42 vaccinated patients (Orgogozo et al 2003; Gilman et al 2005). Despite this trial termination, follow up studies of the Phase IIa trial participants have shown that AN1792 immunization-induced plaque clearance improved neurite abnormalities induced by plaque (Serrano-Pozo et al 2010), although positive anti-amyloid effects did not prevent severity of end-stage dementia nor improved survival (Holmes et al 2008).
Pharmacological Role:	AN-1792 immunization results in the generation of anti-amyloid-beta antibodies, to trigger monocytic/microglial cells to clear amyloid-beta either before deposition, or after plaque formation.
Notes:	Phase IIa clinical trial of this drug ended January 2002.

References

Serrano-Pozo A, William CM, Ferrer I, Uro-Coste E, Delisle MB, Maurage CA, Hock C, Nitsch RM, Masliah E, Growdon JH, Frosch MP, Hyman BT. Beneficial effect of human anti-amyloid-beta active immunization on neurite morphology and tau pathology. Brain. 2010 May;133(Pt 5):1312-27. POW Link

Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal JW, Zotova E, Nicoll JA. Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet. 2008 Jul 19;372(9634):216-23. POW Link

Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, Eisner L, Kirby L, Rovira MB, Forette F, Orgogozo JM; AN1792(QS-21)-201 Study Team. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005 May 10;64(9):1553-62. POW Link

Morgan D, Gitter BD. Evidence supporting a role for anti- Abeta antibodies in the treatment of Alzheimer's disease. Neurobiol Aging. 2004 May-Jun ;25(5):605-8. Abstract

Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC, Jouanny P, Dubois B, Eisner L, Flitman S, Michel BF, Boada M, Frank A, Hock C. Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology. 2003 Jul 8;61(1):46-54. POW Link

Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Liao Z, Lieberburg I, Motter R, Mutter L, Soriano F, Shopp G, Vasquez N, Vandevert C, Walker S, Wogulis M, Yednock T, Games D, Seubert P. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature. 1999 Jul 8;400(6740):173-7. POW Link