Evidence map›Paper›PMID 19638957›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009

Generating differentially targeted amyloid-beta specific intrabodies as a passive vaccination strategy for Alzheimer's disease.

Kelly L Sudol, Michael A Mastrangelo, Wade C Narrow, Maria E Frazer, Yona R Levites, Todd E Golde, Howard J Federoff, William J Bowers

Open access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
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  3. Applying Antibodies Inside Cells: Principles and Recent Advances in Neurobiology, Virology and Oncology.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Kelly L SudolCenter for Neural Development and Disease, University of Rochester Medical Center, Rochester, New York 14642, USA.
Michael A Mastrangelo
Wade C Narrow
Maria E Frazer
Yona R Levites
Todd E Golde
Howard J Federoff
William J Bowers
University of Rochester Medical Center · USJacksonville College · USMayo Clinic in Florida · US

Funding

HSV Amplicon-mediated Disruption of Abeta FibrillogenesisR01AG020204 · NIA · UNIVERSITY OF ROCHESTER · PI FEDEROFF, HOWARD J. · 2003 to 2006
$1.6M
Gene-based TNF-alpha activity modulation in 3xTg-AD miceR01AG026328 · NIA · UNIVERSITY OF ROCHESTER · PI BOWERS, WILLIAM J. · 2007 to 2011
$1.4M
Novel Mouse Model to Dissect Alzheimer's Disease PathophysiologyR01AG023593 · NIA · UNIVERSITY OF ROCHESTER · PI BOWERS, WILLIAM J. · 2004 to 2008
$1.3M
scFv-based Abeta Oligomer Targeting in 3xTg-AD MiceR21AG031878 · NIA · UNIVERSITY OF ROCHESTER · PI BOWERS, WILLIAM J. · 2009 to 2010
$358k
NIA NIH HHS R01 AG020204NIA NIH HHS R01-AG020204NIA NIH HHS R01 AG023593NIA NIH HHS R01-AG023593NIA NIH HHS R01 AG026328NIA NIH HHS R21 AG031878NIA NIH HHS R21-AG031878
6 · The paper itself

Abstract

Amyloid-beta (A beta) has been identified as a key component in Alzheimer's disease (AD). Significant in vitro and human pathological data suggest that intraneuronal accumulation of A beta peptides plays an early role in the neurodegenerative cascade. We hypothesized that targeting an antibody-based therapeutic to specifically abrogate intracellular A beta accumulation could prevent or slow disease onset. A beta 42-specific intracellular antibodies (intrabodies) with and without an intracellular trafficking signal were engineered from a previously characterized single-chain variable fragment (scFv) antibody. The intrabodies, one with an endoplasmic reticulum (ER) targeting signal and one devoid of a targeting sequence, were assessed in cells harboring a doxycycline (Dox)-regulated mutant human amyloid precursor protein Swedish mutant (hAPP(swe)) transcription unit for their abilities to prevent A beta peptide egress. Adeno-associated virus (AAV) vectors expressing the engineered intrabodies were administered to young adult 3xTg-AD mice, a model that develops amyloid and Tau pathologies, prior to the initial appearance of intraneuronal A beta. Chronic expression of the ER-targeted intrabody (IB) led to partial clearance of A beta 42 deposits and interestingly, in reduced staining for a pathologic phospho-Tau epitope (Thr231). This approach may provide insights into the functional relevance of intraneuronal A beta accumulation in early AD and potentially lead to the development of new therapeutics.

Indexed as

VaccinationAlzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsAntibodiesCells, CulturedDependovirusDisease Models, AnimalDoxycyclineEndoplasmic ReticulumGenetic VectorsHumansImmunoglobulin Variable RegionMiceMice, Transgenictau ProteinsAmyloid beta-Protein PrecursorAntibodiesDoxycyclineImmunoglobulin Variable Regiontau Proteins

Identifiers

PMID19638957
PMCPMC2788047
OpenAlexW2071340355

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.