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Anti-Abeta single-chain antibody delivery via adeno-associated virus for treatment of Alzheimer's disease.

Abstract：

:Immunization of mouse models of Alzheimer disease (AD) with amyloid-peptide (Abeta) reduces Abeta deposits and attenuates their memory and learning deficits. Recent clinical trials were halted due to meningoencephalitis, presumably induced by T cell mediated and/or Fc-mediated immune responses. Because injection of anti-Abeta F(ab')(2) antibodies also induces clearance of amyloid plaques in AD mouse models, we have tested a novel gene therapy modality where an adeno-associated virus (AAV) encoding anti-Abeta single-chain antibody (scFv) is injected into the corticohippocampal regions of AD mouse models. One year after injection, expression of scFv was readily detectable in the neurons of the hippocampus without discernible neurotoxicity. AD mouse models subjected to AAV injection had much less amyloid deposits at the injection sites than the mouse models subjected to PBS injection. Because the scFv lacks the Fc portion of the immunoglobulin molecule, this modality may be a feasible solution for AD without eliciting inflammation.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Fukuchi K,Tahara K,Kim HD,Maxwell JA,Lewis TL,Accavitti-Loper MA,Kim H,Ponnazhagan S,Lalonde R

doi

10.1016/j.nbd.2006.04.012

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

502-11

issue

3

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(06)00091-X

journal_volume

23

pub_type

杂志文章

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