Gene delivery of a modified antibody to Aβ reduces progression of murine Alzheimer’s disease

Clicks: 326
ID: 268196
2019
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #747 of 2,056 articles by views in PloS one

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 2,056 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Antibody therapies for Alzheimer’s Disease (AD) hold promise but have been limited by the inability of these proteins to migrate efficiently across the blood brain barrier (BBB). Central nervous system (CNS) gene transfer by vectors like adeno-associated virus (AAV) overcome this barrier by allowing the bodies’ own cells to produce the therapeutic protein, but previous studies using this method to target amyloid-β have shown success only with truncated single chain antibodies (Abs) lacking an Fc domain. The Fc region mediates effector function and enhances antigen clearance from the brain by neonatal Fc receptor (FcRn)-mediated reverse transcytosis and is therefore desirable to include for such treatments. Here, we show that single chain Abs fused to an Fc domain retaining FcRn binding, but lacking Fc gamma receptor (FcγR) binding, termed a silent scFv-IgG, can be expressed and released into the CNS following gene transfer with AAV. While expression of canonical IgG in the brain led to signs of neurotoxicity, this modified Ab was efficiently secreted from neuronal cells and retained target specificity. Steady state levels in the brain exceeded peak levels obtained by intravenous injection of IgG. AAV-mediated expression of this scFv-IgG reduced cortical and hippocampal plaque load in a transgenic mouse model of progressive β-amyloid plaque accumulation. These findings suggest that CNS gene delivery of a silent anti-Aβ scFv-IgG was well-tolerated, durably expressed and functional in a relevant disease model, demonstrating the potential of this modality for the treatment of Alzheimer’s disease.
Reference Key
elmer2019plosgene Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Bradford M. Elmer;Kurt A. Swanson;Dinesh S. Bangari;Peter A. Piepenhagen;Errin Roberts;Tatyana Taksir;Lei Guo;Maria-Carmen Obinu;Pascal Barneoud;Susan Ryan;Bailin Zhang;Laurent Pradier;Zhi-Yong Yang;Gary J. Nabel;
Journal PloS one
Year 2019
DOI
10.1371/journal.pone.0226245
URL
http://dx.plos.org/10.1371/journal.pone.0226245
Keywords
central nervous system hippocampus alzheimer's disease mouse models enzyme-linked immunoassays immunohistochemistry techniques intravenous injections amyloid plaques

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.