title: Prophylaxis and treatment of Alzheimer's disease by delivery of an adeno-associated virus encoding a monoclonal antibody targeting the amyloid Beta protein.
abstract: We previously reported on a monoclonal antibody (mAb) that targeted amyloid beta (Aß) protein. Repeated injection of that mAb reduced the accumulation of Aß protein in the brain of human Aß transgenic mice (Tg2576). In the present study, cDNA encoding the heavy and light chains of this mAb were subcloned into an adeno-associated virus type 1 (AAV) vector with a 2A/furin adapter. A single intramuscular injection of 3.0×10(10) viral genome of these AAV vectors into C57BL/6 mice generated serum anti-Aß Ab levels up to 0.3 mg/ml. Anti-Aß Ab levels in excess of 0.1 mg/ml were maintained for up to 64 weeks. The effect of AAV administration on Aß levels in vivo was examined. A significant decrease in Aß levels in the brain of Tg2576 mice treated at 5 months (prophylactic) or 10 months (therapeutic) of age was observed. These results support the use of AAV vector encoding anti-Aß Ab for the prevention and treatment of Alzheimer's disease.
authors.affiliation: Department of Molecular Biodefense Research, Yokohama City University, Yokohama, Kanagawa, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Shimada
authors.forename: Shinya
authors.initials: S
authors.lastname: Abe
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Shiozaki
authors.forename: Mitsue
authors.initials: M
authors.lastname: Okuda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Okuda
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics; D000229:Dependovirus; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D057127:Single-Chain Antibodies / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D057127:Single-Chain Antibodies; C075222:amyloid beta-protein (1-42)
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