Evidence map›Paper›PMID 24196577›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014

Plasmapheresis eliminates the negative impact of AAV antibodies on microdystrophin gene expression following vascular delivery.

L G Chicoine, C L Montgomery, W G Bremer, K M Shontz, D A Griffin, K N Heller, S Lewis, V Malik, W E Grose, C J Shilling and 9 more

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

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 2 pooled it
6.0field-weighted citation impact, top 4% 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

114 citing papers in PubMed, 2 syntheses or guidelines pooled it, 155 citations in OpenAlex.

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  17. Nonclinical strategies and considerations to enable the redosing of gene therapies.Molecular therapy. Methods & clinical development · 2025
    Review
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54 more citing papers are in PubMed but not listed here.

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

19 authors at 2 institutions in 1 country.

L G ChicoineDepartment of Pediatrics, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, USA; Centers for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; Integrated Biomedical Science Graduate Program, College of Medicine, The Ohio State University, Columbus, Ohio, USA. Electronic address: Louis.Chicoine@nationwidechildrens.org.
C L MontgomeryCenters for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
W G BremerVaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
K M ShontzCenters for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
D A GriffinCenters for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
K N HellerCenters for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; Molecular, Cellular & Developmental Biology Graduate Program, The Ohio State University, Columbus, Ohio, USA.
S LewisCenters for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
V MalikCenters for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
W E GroseCenters for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
C J ShillingCenters for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
K J CampbellVaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
T J PrestonDepartment of Pediatrics, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, USA.
B D ColeyDepartment of Pediatrics, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, USA.
P T MartinDepartment of Pediatrics, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, USA; Centers for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; Integrated Biomedical Science Graduate Program, College of Medicine, The Ohio State University, Columbus, Ohio, USA; Molecular, Cellular & Developmental Biology Graduate Program, The Ohio State University, Columbus, Ohio, USA.
C M WalkerDepartment of Pediatrics, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, USA; Integrated Biomedical Science Graduate Program, College of Medicine, The Ohio State University, Columbus, Ohio, USA; Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; Molecular, Cellular & Developmental Biology Graduate Program, The Ohio State University, Columbus, Ohio, USA.
K R ClarkDepartment of Pediatrics, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, USA; Centers for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; Molecular, Cellular & Developmental Biology Graduate Program, The Ohio State University, Columbus, Ohio, USA.
Z SahenkDepartment of Pediatrics, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, USA; Centers for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; Department of Neurology, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, USA.
J R MendellDepartment of Pediatrics, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, USA; Centers for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; Integrated Biomedical Science Graduate Program, College of Medicine, The Ohio State University, Columbus, Ohio, USA; Molecular, Cellular & Developmental Biology Graduate Program, The Ohio State University, Columbus, Ohio, USA; Department of Neurology, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, USA. Electronic address: Jerry.Mendell@nationwidechildrens.org.
L R Rodino-KlapacDepartment of Pediatrics, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, USA; Centers for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; Integrated Biomedical Science Graduate Program, College of Medicine, The Ohio State University, Columbus, Ohio, USA; Molecular, Cellular & Developmental Biology Graduate Program, The Ohio State University, Columbus, Ohio, USA. Electronic address: Louise.Rodino-Klapac@nationwidechildrens.org.
Nationwide Children's Hospital · USThe Ohio State University · US

Funding

Vector Production CoreU54NS055958 · NINDS · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI MENDELL, JERRY ROY · 2007 to 2010
$7.9M
Training and Education CoreU54HD066409 · NICHD · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI MARTIN, PAUL TAYLOR · 2010 to 2014
$6.7M
Dystrophin restoration in two animal models of Duchenne Muscular DystrophyF32AR055008 · NIAMS · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI RODINO-KLAPAC, LOUISE R. · 2007 to 2009
$148k
NIAMS NIH HHS 1F32AR055008NIAMS NIH HHS F32 AR055008NICHD NIH HHS 1U54HD066409NICHD NIH HHS U54 HD066409NINDS NIH HHS 1U54NS055958-01A1NINDS NIH HHS U54 NS055958
6 · The paper itself

Abstract

Duchenne muscular dystrophy is a monogenic disease potentially treatable by gene replacement. Use of recombinant adeno-associated virus (AAV) will ultimately require a vascular approach to broadly transduce muscle cells. We tested the impact of preexisting AAV antibodies on microdystrophin expression following vascular delivery to nonhuman primates. Rhesus macaques were treated by isolated limb perfusion using a fluoroscopically guided catheter. In addition to serostatus stratification, the animals were placed into one of the three immune suppression groups: no immune suppression, prednisone, and triple immune suppression (prednisone, tacrolimus, and mycophenolate mofetil). The animals were analyzed for transgene expression at 3 or 6 months. Microdystrophin expression was visualized in AAV, rhesus serotype 74 sero-negative animals (mean: 48.0 ± 20.8%) that was attenuated in sero-positive animals (19.6 ± 18.7%). Immunosuppression did not affect transgene expression. Importantly, removal of AAV binding antibodies by plasmapheresis in AAV sero-positive animals resulted in high-level transduction (60.8 ± 18.0%), which is comparable with that of AAV sero-negative animals (53.7 ± 7.6%), whereas non-pheresed sero-positive animals demonstrated significantly lower transduction levels (10.1 ± 6.0%). These data support the hypothesis that removal of AAV binding antibodies by plasmapheresis permits successful and sustained gene transfer in the presence of preexisting immunity (natural infection) to AAV.

Indexed as

Gene ExpressionPlasmapheresisAnimalsAntibodies, NeutralizingAntibodies, ViralDependovirusDystrophinGenes, ReporterGenetic VectorsGreen Fluorescent ProteinsHumansMacaca mulattaMaleMuscle, SkeletalTransduction, GeneticTransgenesAntibodies, NeutralizingAntibodies, ViralDystrophinenhanced green fluorescent proteinGreen Fluorescent Proteins

Identifiers

PMID24196577
PMCPMC3916040
OpenAlexW2009247311

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.