Evidence map›Paper›PMID 28958576›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017

Guanidinylated Neomycin Conjugation Enhances Intranasal Enzyme Replacement in the Brain.

Wenyong Tong, Chrissa A Dwyer, Bryan E Thacker, Charles A Glass, Jillian R Brown, Kristina Hamill, Kelley W Moremen, Stéphane Sarrazin, Philip L S M Gordts, Lara E Dozier and 3 more

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

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.3field-weighted citation impact, top 45% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
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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

13 authors at 2 institutions in 1 country.

Wenyong TongDepartment of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093-0687, USA.
Chrissa A DwyerDepartment of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093-0687, USA.
Bryan E ThackerTEGA Therapeutics, Inc., 9500 Gilman Drive, La Jolla, CA 92093-0713, USA.
Charles A GlassTEGA Therapeutics, Inc., 9500 Gilman Drive, La Jolla, CA 92093-0713, USA.
Jillian R BrownTEGA Therapeutics, Inc., 9500 Gilman Drive, La Jolla, CA 92093-0713, USA.
Kristina HamillDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0358, USA.
Kelley W MoremenDepartment of Biochemistry, Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
Stéphane SarrazinDepartment of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093-0687, USA.
Philip L S M GordtsDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093-0687, USA.
Lara E DozierSection of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0366 USA.
Gentry N PatrickSection of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0366 USA.
Yitzhak TorDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0358, USA.
Jeffrey D EskoDepartment of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093-0687, USA. Electronic address: jesko@ucsd.edu.
University of California, San Diego · USUniversity of Georgia · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
TR&D3. Approaches to Proteoglycan Function at Biochemical and Cellular LevelsP41GM103390 · NIGMS · UNIVERSITY OF GEORGIA · PI MOREMEN, KELLEY W. · 2012 to 2019
$14.5M
Blood Cells in Hemostasis and ThrombosisT32HL086344 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 2008 to 2023
$4.4M
Drug Discovery for Multiple Hereditary ExostosesR01AR064202 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D · 2013 to 2017
$1.9M
Intranasal Sulfamidase Delivery to the BrainR43NS089383 · NINDS · TEGA THERAPEUTICS, INC. · PI GLASS, CHARLES ALEXANDER · 2015 to 2015
$237k
NCI NIH HHS P30 CA023100NHLBI NIH HHS T32 HL086344NIAMS NIH HHS R01 AR064202NIGMS NIH HHS P41 GM103390NINDS NIH HHS R43 NS089383
6 · The paper itself

Abstract

Iduronidase (IDUA)-deficient mice accumulate glycosaminoglycans in cells and tissues and exhibit many of the same neuropathological symptoms of patients suffering from Mucopolysaccharidosis I. Intravenous enzyme-replacement therapy for Mucopolysaccharidosis I ameliorates glycosaminoglycan storage and many of the somatic aspects of the disease but fails to treat neurological symptoms due to poor transport across the blood-brain barrier. In this study, we examined the delivery of IDUA conjugated to guanidinoneomycin (GNeo), a molecular transporter. GNeo-IDUA and IDUA injected intravenously resulted in reduced hepatic glycosaminoglycan accumulation but had no effect in the brain due to fast clearance from the circulation. In contrast, intranasally administered GNeo-IDUA entered the brain rapidly. Repetitive intranasal treatment with GNeo-IDUA reduced glycosaminoglycan storage, lysosome size and number, and neurodegenerative astrogliosis in the olfactory bulb and primary somatosensory cortex, whereas IDUA was less effective. The enhanced efficacy of GNeo-IDUA was not the result of increased nose-to-brain delivery or enzyme stability, but rather due to more efficient uptake into neurons and astrocytes. GNeo conjugation also enhanced glycosaminoglycan clearance by intranasally delivered sulfamidase to the brain of sulfamidase-deficient mice, a model of Mucopolysaccharidosis IIIA. These findings suggest the general utility of the guanidinoglycoside-based delivery system for restoring missing lysosomal enzymes in the brain.

Indexed as

Administration, IntranasalAnimalsBiomarkersBrainCerebral CortexEnzyme Replacement TherapyGliosisGlycosaminoglycansHumansHydrolasesIduronidaseLiverLysosomesMiceMice, KnockoutNeomycinBiomarkersGlycosaminoglycansHydrolasesIduronidaseNeomycinN-sulfoglucosamine sulfohydrolaseenzyme-replacement therapyguanidinoglycosidesintranasal deliverymucopolysaccharidosesneuropathology

Identifiers

PMID28958576
PMCPMC5768556
OpenAlexW2747176279

What OpenQuestion holds

Textmetadata
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.