Evidence map›Paper›PMID 32911688›Full record

ArticlePharmaceutics2020

Acute and Chronic Dosing of a High-Affinity Rat/Mouse Chimeric Transferrin Receptor Antibody in Mice.

Demi M Castellanos, Jiahong Sun, Joshua Yang, Weijun Ou, Alexander C Zambon, William M Pardridge, Rachita K Sumbria

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.3field-weighted citation impact, top 16% 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

15 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Bispecific brain-penetrant antibodies for treatment of Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025
    Review
  6. Article
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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

7 authors at 3 institutions in 1 country.

Demi M CastellanosHenry E. Riggs School of Applied Life Sciences, Keck Graduate Institute, Claremont, CA 91711, USA.ORCID 0000-0001-7460-5326
Jiahong SunDepartment of Biopharmaceutical Sciences, School of Pharmacy and Health Sciences, Keck Graduate Institute, Claremont, CA 91711, USA.
Joshua YangHenry E. Riggs School of Applied Life Sciences, Keck Graduate Institute, Claremont, CA 91711, USA.
Weijun OuDepartment of Biopharmaceutical Sciences, School of Pharmacy and Health Sciences, Keck Graduate Institute, Claremont, CA 91711, USA.
Alexander C ZambonDepartment of Biopharmaceutical Sciences, School of Pharmacy and Health Sciences, Keck Graduate Institute, Claremont, CA 91711, USA.
William M PardridgeDepartment of Medicine, University of California, Los Angeles, CA 90095, USA.
Rachita K SumbriaDepartment of Biopharmaceutical Sciences, School of Pharmacy and Health Sciences, Keck Graduate Institute, Claremont, CA 91711, USA.ORCID 0000-0002-7459-0723
Keck Graduate Institute · USUniversity of California, Irvine · USUniversity of California, Los Angeles · US

Funding

A Brain Penetrating Bi-functional Transferrin Receptor Antibody-TNF-alpha Decoy Receptor Fusion Protein for Alzheimer's DiseaseR01AG062840 · NIA · KECK GRADUATE INST OF APPLIED LIFE SCIS · PI SUMBRIA, RACHITA · 2019 to 2024
$1.9M
Re-engineering Erythropoietin for Alzheimer's DiseaseR21AG055949 · NIA · KECK GRADUATE INST OF APPLIED LIFE SCIS · PI SUMBRIA, RACHITA · 2017 to 2018
$382k
Joseph H. Stahlberg Foundation NANIA NIH HHS R01 AG062840NIA NIH HHS R21 AG055949NIH HHS R01AG062840NIH HHS R21AG055949
6 · The paper itself

Abstract

Non-invasive brain delivery of neurotherapeutics is challenging due to the blood-brain barrier. The revived interest in transferrin receptor antibodies (TfRMAbs) as brain drug-delivery vectors has revealed the effect of dosing regimen, valency, and affinity on brain uptake, TfR expression, and Fc-effector function side effects. These studies have primarily used monovalent TfRMAbs with a human constant region following acute intravenous dosing in mice. The effects of a high-affinity bivalent TfRMAb with a murine constant region, without a fusion partner, following extravascular dosing in mice are, however, not well characterized. Here we elucidate the plasma pharmacokinetics and safety of a high-affinity bivalent TfRMAb with a murine constant region following acute and chronic subcutaneous dosing in adult C57BL/6J male mice. Mice received a single (acute dosing) 3 mg/kg dose, or were treated for four weeks (chronic dosing). TfRMAb and control IgG1 significantly altered reticulocyte counts following acute and chronic dosing, while other hematologic parameters showed minimal change. Chronic TfRMAb dosing did not alter plasma- and brain-iron measurements, nor brain TfR levels, however, it significantly increased splenic-TfR and -iron. Plasma concentrations of TfRMAb were significantly lower in mice chronically treated with IgG1 or TfRMAb. Overall, no injection related reactions were observed in mice.

Indexed as

blood-brain barrierironpharmacokineticsreticulocytestransferrin receptortransferrin receptor monoclonal antibody

Identifiers

PMID32911688
PMCPMC7558337
OpenAlexW3083774881

What OpenQuestion holds

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LicenceCC BY
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.