Evidence map›Paper›PMID 23410508›Full record

ArticleMolecular pharmaceutics2013

Pharmacokinetics and brain uptake of an IgG-TNF decoy receptor fusion protein following intravenous, intraperitoneal, and subcutaneous administration in mice.

Rachita K Sumbria, Qing-Hui Zhou, Eric Ka-Wai Hui, Jeff Zhiqiang Lu, Ruben J Boado, William M Pardridge

Open access · greenAbstract read
In one paragraph

Article in Molecular pharmaceutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.9field-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

24 citing papers in PubMed, 43 citations in OpenAlex.

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  19. A New Venue of TNF Targeting.International journal of molecular sciences · 2018
    Review
  20. Bidirectional apical-basal traffic of the cation-independent mannose-6-phosphate receptor in brain endothelial cells.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017
    Article
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 2 institutions in 1 country.

Rachita K SumbriaDepartment of Medicine, UCLA, Los Angeles, California 90024, USA.
Qing-Hui Zhou
Eric Ka-Wai Hui
Jeff Zhiqiang Lu
Ruben J Boado
William M Pardridge
University of California, Los Angeles · USArmaGen (United States) · US

Funding

Monoclonal Antibody Drug Development for Alzheimer?s DiseaseR01AG032244 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PARDRIDGE, WILLIAM M · 2008 to 2012
$1.6M
NIA NIH HHS R01 AG032244NIA NIH HHS R01-AG032244
6 · The paper itself

Abstract

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine active in the brain. Etanercept, the TNF decoy receptor (TNFR), does not cross the blood-brain barrier (BBB). The TNFR was re-engineered for BBB penetration as a fusion protein with a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR), and this fusion protein is designated cTfRMAb-TNFR. The cTfRMAb domain of the fusion protein acts as a molecular Trojan horse and mediates transport via the endogenous BBB TfR. To support future chronic treatment of mouse models of neural disease with daily administration of the cTfRMAb-TNFR fusion protein, a series of pharmacokinetics and brain uptake studies in the mouse was performed. The cTfRMAb-TNFR fusion protein was radiolabeled and injected into mice via the intravenous, intraperitoneal (IP), or subcutaneous (SQ) routes of administration at doses ranging from 0.35 to 10 mg/kg. The distribution of the fusion protein into plasma following the IP or SQ routes was enhanced by increasing the injection dose from 3 to 10 mg/kg. The fusion protein demonstrated long circulation times with high metabolic stability following the IP or SQ routes of injection. The IP or SQ routes produced concentrations of the cTfRMAb-TNFR fusion protein in the brain that exceed by 20- to 50-fold the concentration of TNFα in pathologic conditions of the brain. The SQ injection is the preferred route of administration, as the level of cTfRMAb fusion protein produced in the brain is comparable to that generated with intravenous injection, and at a much lower plasma area under the concentration curve of the fusion protein as compared to IP administration.

Indexed as

AnimalsAntibodies, MonoclonalArea Under CurveBlood-Brain BarrierBrainDrug DesignEtanerceptImmunoglobulin GInflammationInfusions, IntravenousInfusions, ParenteralInfusions, SubcutaneousMaleMiceMice, Inbred C57BLReceptors, TransferrinAntibodies, MonoclonalEtanerceptImmunoglobulin GReceptors, TransferrinReceptors, Tumor Necrosis FactorRecombinant Fusion Proteins

Identifiers

PMID23410508
PMCPMC3615110
OpenAlexW2009918976

What OpenQuestion holds

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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.