Evidence map›Paper›PMID 24846143›Full record

ArticlePloS one2014

Delayed administration of a bio-engineered zinc-finger VEGF-A gene therapy is neuroprotective and attenuates allodynia following traumatic spinal cord injury.

Sarah A Figley, Yang Liu, Spyridon K Karadimas, Kajana Satkunendrarajah, Peter Fettes, S Kaye Spratt, Gary Lee, Dale Ando, Richard Surosky, Martin Giedlin and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.4field-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

20 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
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  7. Brain & spine · 2022
    Review
  8. Genome Editing for CNS Disorders.Frontiers in neuroscience · 2020
    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

11 authors at 3 institutions in 2 countries.

Sarah A FigleyDepartment of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
Yang LiuDepartment of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario, Canada.
Spyridon K KaradimasDepartment of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
Kajana SatkunendrarajahDepartment of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario, Canada.
Peter FettesDepartment of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario, Canada.
S Kaye SprattDepartment of Therapeutic Development, Sangamo BioSciences, Pt. Richmond, California, United States of America.
Gary LeeDepartment of Therapeutic Development, Sangamo BioSciences, Pt. Richmond, California, United States of America.
Dale AndoDepartment of Therapeutic Development, Sangamo BioSciences, Pt. Richmond, California, United States of America.
Richard SuroskyDepartment of Therapeutic Development, Sangamo BioSciences, Pt. Richmond, California, United States of America.
Martin GiedlinInstitute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
Michael G FehlingsDepartment of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
University Health Network · CASangamo BioSciences (United States) · USUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Following spinal cord injury (SCI) there are drastic changes that occur in the spinal microvasculature, including ischemia, hemorrhage, endothelial cell death and blood-spinal cord barrier disruption. Vascular endothelial growth factor-A (VEGF-A) is a pleiotropic factor recognized for its pro-angiogenic properties; however, VEGF has recently been shown to provide neuroprotection. We hypothesized that delivery of AdV-ZFP-VEGF--an adenovirally delivered bio-engineered zinc-finger transcription factor that promotes endogenous VEGF-A expression--would result in angiogenesis, neuroprotection and functional recovery following SCI. This novel VEGF gene therapy induces the endogenous production of multiple VEGF-A isoforms; a critical factor for proper vascular development and repair. Briefly, female Wistar rats--under cyclosporin immunosuppression--received a 35 g clip-compression injury and were administered AdV-ZFP-VEGF or AdV-eGFP at 24 hours post-SCI. qRT-PCR and Western Blot analysis of VEGF-A mRNA and protein, showed significant increases in VEGF-A expression in AdV-ZFP-VEGF treated animals (p<0.001 and p<0.05, respectively). Analysis of NF200, TUNEL, and RECA-1 indicated that AdV-ZFP-VEGF increased axonal preservation (p<0.05), reduced cell death (p<0.01), and increased blood vessels (p<0.01), respectively. Moreover, AdV-ZFP-VEGF resulted in a 10% increase in blood vessel proliferation (p<0.001). Catwalk™ analysis showed AdV-ZFP-VEGF treatment dramatically improves hindlimb weight support (p<0.05) and increases hindlimb swing speed (p<0.02) when compared to control animals. Finally, AdV-ZFP-VEGF administration provided a significant reduction in allodynia (p<0.01). Overall, the results of this study indicate that AdV-ZFP-VEGF administration can be delivered in a clinically relevant time-window following SCI (24 hours) and provide significant molecular and functional benefits.

Indexed as

AdenoviridaeZinc FingersAnimalsFemaleGenetic TherapyHEK293 CellsHumansHyperalgesiaNeovascularization, PhysiologicRatsRats, WistarSpinal Cord InjuriesVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Avascular endothelial growth factor A, rat

Identifiers

PMID24846143
PMCPMC4028194
OpenAlexW2132049003

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.