Evidence map›Paper›PMID 28624473›Full record

ArticleBiochimica et biophysica acta. General subjects2017

Antibody blood-brain barrier efflux is modulated by glycan modification.

John M Finke, Kari R Ayres, Ryan P Brisbin, Hali A Hill, Emily E Wing, William A Banks

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochimica et biophysica acta. General subjects, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

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  8. Neurotheranostics as personalized medicines.Advanced drug delivery reviews · 2019
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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

6 authors at 3 institutions in 1 country.

John M FinkeDivision of Sciences and Mathematics, Interdisciplinary Arts and Sciences, University of Washington Tacoma, Tacoma, WA, USA. Electronic address: jfinke@u.washington.edu.
Kari R AyresDivision of Sciences and Mathematics, Interdisciplinary Arts and Sciences, University of Washington Tacoma, Tacoma, WA, USA.
Ryan P BrisbinDivision of Sciences and Mathematics, Interdisciplinary Arts and Sciences, University of Washington Tacoma, Tacoma, WA, USA.
Hali A HillDivision of Sciences and Mathematics, Interdisciplinary Arts and Sciences, University of Washington Tacoma, Tacoma, WA, USA.
Emily E WingGeriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.
William A BanksGeriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Geriatric Medicine, University of Washington School of Medicine, Seattle, WA, USA.
University of Washington Tacoma · USUniversity of Washington · USVA Puget Sound Health Care System · US

Funding

Modulation of IgG blood-brain barrier permeability by surface-accessible glycan moietiesR03AG050184 · NIA · UNIVERSITY OF WASHINGTON · PI BANKS, WILLIAM A, FINKE, JOHN MASON · 2015 to 2016
$160k
NIA NIH HHS R03 AG050184
6 · The paper itself

Abstract

backgroundDrug delivery to the brain is a major roadblock to treatment of Alzheimer's disease. Recent results of the PRIME study indicate that increasing brain penetration of antibody drugs improves Alzheimer's treatment outcomes. New approaches are needed to better accomplish this goal. Based on prior evidence, the hypothesis that glycan modification alters antibody blood-brain barrier permeability was tested here.

methodsThe blood-brain barrier permeability coefficient Pe of different glycosylated states of anti-amyloid IgG was measured using in vitro models of brain microvascular endothelial cells. Monoclonal antibodies 4G8, with sialic acid, and 6E10, lacking sialic acid, were studied. The amount of sialic acid was determined using quantitative and semi-quantitative surface plasmon resonance methods.

resultsInflux of IgG was not saturable and was largely insensitive to IgG species and glycosylation state. By contrast, efflux of 4G8 efflux was significantly lower than both albumin controls and 6E10. Removal of α2,6-linked sialic acid group present on 12% of 4G8 completely restored efflux to that of 6E10 but increasing the α2,6-sialylated fraction to 15% resulted in no change. Removal of the Fc glycan from 4G8 partially restored efflux. Alternate sialic acid groups with α2,3 and α2,8 linkages, nor on the Fc glycan, were not detected at significant levels on either 4G8 or 6E10.

conclusionsThese results support a model in which surface-sialylated 4G8 inhibits its own efflux and that of asialylated 4G8. GENERAL SIGNIFICANCE: Glycan modification has the potential to increase antibody drug penetration into the brain through efflux inhibition.

Indexed as

Blood-Brain BarrierAnimalsAntibodies, MonoclonalGlycosylationImmunoglobulin GMaleMiceN-Acetylneuraminic AcidAntibodies, MonoclonalImmunoglobulin GN-Acetylneuraminic AcidAlzheimer's diseaseBlood brain barrierFab Fc antibody glycosylationSialic acidSurface plasmon resonance

Identifiers

PMID28624473
PMCPMC5557653
OpenAlexW2626841794

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.