Evidence map›Paper›PMID 34205013›Full record

ArticlePharmaceuticals (Basel, Switzerland)2021

Mathematical Models of Blood-Brain Barrier Transport of Monoclonal Antibodies Targeting the Transferrin Receptor and the Insulin Receptor.

William M Pardridge, Tom Chou

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

Article in Pharmaceuticals (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.4field-weighted citation impact, top 8% 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

21 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Review
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

2 authors at 1 institution in 1 country.

William M PardridgeDepartment of Medicine, UCLA, Los Angeles, CA 90095, USA.ORCID 0000-0002-2664-1338
Tom ChouDepartments of Computational Medicine and Mathematics, UCLA, Los Angeles, CA 90095, USA.ORCID 0000-0003-0785-6349
University of California, Los Angeles · US

Funding

Tracking clonal dynamics during hematopoiesis: mechanistic insight via modeling and data analysisR01HL146552 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHOU, TOM · 2019 to 2022
$907k
NHLBI NIH HHS R01 HL146552NIH HHS R01HL146552NSF DMS-1814364
6 · The paper itself

Abstract

We develop and analyze mathematical models for receptor-mediated transcytosis of monoclonal antibodies (MAb) targeting the transferrin receptor (TfR) or the insulin receptor (IR), which are expressed at the blood-brain barrier (BBB). The mass-action kinetic model for both the TfR and IR antibodies were solved numerically to generate predictions for the concentrations of all species in all compartments considered. Using these models, we estimated the rates of MAb endocytosis into brain capillary endothelium, which forms the BBB in vivo, the rates of MAb exocytosis from the intra-endothelial compartment into brain extracellular space, and the rates of receptor recycling from the endothelial space back to the luminal endothelial plasma membrane. Our analysis highlights the optimal rates of MAb association with the targeted receptor. An important role of the endogenous ligand, transferrin (Tf) or insulin, in receptor-mediated-transport (RMT) of the associated MAb was found and was attributed to the five order magnitude difference between plasma concentrations of Tf (25,000 nM) and insulin (0.3 nM). Our modeling shows that the very high plasma concentration of Tf leads to only 5% of the endothelial TfR expressed on the luminal endothelial membrane.

Indexed as

biologicsblood-brain barrierbrain drug deliveryinsulin receptormonoclonal antibodytransferrin receptor

Identifiers

PMID34205013
PMCPMC8226686
OpenAlexW3172790770

What OpenQuestion holds

Textmetadata
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.