Evidence map›Paper›PMID 21351076›Full record

ArticleBiotechnology and bioengineering2011

Expression in CHO cells and pharmacokinetics and brain uptake in the Rhesus monkey of an IgG-iduronate-2-sulfatase fusion protein.

Jeff Zhiqiang Lu, Ruben J Boado, Eric K-W Hui, Qing-Hui Zhou, William M Pardridge

Abstract read
In one paragraph

Article in Biotechnology and bioengineering, 2011. 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
2.8field-weighted citation impact, top 10% 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, 38 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Jeff Zhiqiang LuArmaGen Technologies, Inc, Santa Monica, California, USA.
Ruben J Boado
Eric K-W Hui
Qing-Hui Zhou
William M Pardridge
University of California, Los Angeles · USArmaGen (United States) · US

Funding

Enzyme replacement therapy of the brain in Mucopolysaccharidosis Type IIR43NS067707 · NINDS · ARMAGEN TECHNOLOGIES, INC. · PI LU, ZHIQIANG · 2011 to 2011
$111k
NINDS NIH HHS R43 NS067707NINDS NIH HHS R43-NS-067707-0PHS HHS CJX1-443835-WS-29646
6 · The paper itself

Abstract

Sulfatases are potential therapeutic biopharmaceuticals, as mutations in sulfatase genes leads to inherited disease. Mucopolysaccharidosis (MPS) Type II is caused by mutations in the lysosomal enzyme, iduronate-2-sulfatase (IDS). MPS-II affects the brain and enzyme replacement therapy is ineffective for the brain, because IDS does not cross the blood-brain barrier (BBB). To deliver IDS across the human BBB, the sulfatase has been re-engineered as an IgG-sulfatase fusion protein with a genetically engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb part of the HIRMAb-IDS fusion protein acts as a molecular Trojan horse to ferry the fused IDS across the BBB. Chinese hamster ovary (CHO) cells were stably transfected to produce the HIRMAb-IDS fusion protein. The fusion protein was triaged to the lysosomal compartment of MPS-II fibroblasts based on confocal microscopy, and 300 ng/mL medium concentrations normalized IDS enzyme activity in the cells. The HIRMAb-IDS fusion protein was tritiated and injected intravenously into the adult Rhesus monkey at a low dose of 0.1 mg/kg. The IDS enzyme activity in plasma was elevated 10-fold above the endogenous level, and therapeutic plasma concentrations were generated in vivo. The uptake of the HIRMAb-IDS fusion protein in the brain was sufficiently high to produce therapeutic concentrations of IDS in the brain following IV administration of the fusion protein.

Indexed as

AnimalsAntibodies, MonoclonalBrainCell LineCricetinaeCricetulusFibroblastsGene ExpressionHumansIduronate SulfataseImmunoglobulin GInjections, IntravenousLysosomesMacaca mulattaReceptor, InsulinRecombinant Fusion ProteinsAntibodies, MonoclonalIduronate SulfataseImmunoglobulin GReceptor, InsulinRecombinant Fusion Proteins

Identifiers

PMID21351076
PMCPMC3117053
OpenAlexW1974491241

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.