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.
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.
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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.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Article
- AAV Vector-Mediated Antibody Delivery (A-MAD) in the Central Nervous System.Frontiers in neurology · 2022Review
- Applying Antibodies Inside Cells: Principles and Recent Advances in Neurobiology, Virology and Oncology.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020Review
- Engineered Extracellular Vesicles/Exosomes as a New Tool against Neurodegenerative Diseases.Pharmaceutics · 2020Review
- Adeno-associated virus-based Alzheimer's disease mouse models and potential new therapeutic avenues.British journal of pharmacology · 2019Review
- Gene delivery of a modified antibody to Aβ reduces progression of murine Alzheimer's disease.PloS one · 2019Article
- Noninvasive 40-Hz light flicker to recruit microglia and reduce amyloid beta load.Nature protocols · 2018Article
- Neuro-Immuno-Gene- and Genome-Editing-Therapy for Alzheimer's Disease: Are We There Yet?Journal of Alzheimer's disease : JAD · 2018Review
- State of play and clinical prospects of antibody gene transfer.Journal of translational medicine · 2017Review
- Recombinant Antibody Fragments for Neurodegenerative Diseases.Current neuropharmacology · 2017Review
- Antibodies inside of a cell can change its outside: Can intrabodies provide a new therapeutic paradigm?Computational and structural biotechnology journal · 2016Review
- Functional inhibition of β-catenin-mediated Wnt signaling by intracellular VHH antibodies.mAbs · 2015Article
- Review
- RANGE: Gene Transfer of Reversibly Controlled Polycistronic Genes.Molecular therapy. Nucleic acids · 2013Article
- Article
- Evidence for prion-like mechanisms in several neurodegenerative diseases: potential implications for immunotherapy.Clinical & developmental immunology · 2013Review
- Engineered antibody therapies to counteract mutant huntingtin and related toxic intracellular proteins.Progress in neurobiology · 2012Review
- Anti-Amyloid-β Single-Chain Antibody Brain Delivery Via AAV Reduces Amyloid Load But May Increase Cerebral Hemorrhages in an Alzheimer's Disease Mouse Model.Journal of Alzheimer's disease : JAD · 2011Article
- Article
- Early oligodendrocyte/myelin pathology in Alzheimer's disease mice constitutes a novel therapeutic target.The American journal of pathology · 2010Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
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.
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Registered trials
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.