Evidence map›Paper›PMID 19571887›Full record

ArticleGene therapy2009

Immunological priming potentiates non-viral anti-inflammatory gene therapy treatment of neuropathic pain.

E Sloane, S Langer, B Jekich, J Mahoney, T Hughes, M Frank, W Seibert, G Huberty, B Coats, J Harrison and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.4field-weighted citation impact, top 24% 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

22 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Mesoporous silica-supported lipid bilayers (protocells) for DNA cargo delivery to the spinal cord.Journal of controlled release : official journal of the Controlled Release Society · 2013
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  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

18 authors at 5 institutions in 2 countries.

E SloaneUniversity of Colorado, Boulder, CO, USA.
S Langer
B Jekich
J Mahoney
T Hughes
M Frank
W Seibert
G Huberty
B Coats
J Harrison
D Klinman
S Poole
S Maier
K Johnson
R Chavez
L R Watkins
L Leinwand
E Milligan
University of Colorado Boulder · USEpigen Biosciences (United States) · USNational Cancer Institute · USNational Institute for Biological Standards and Control · GBUniversity of New Mexico · US

Funding

Mechanism of action and therapeutic utility of stimulatory CpG oligonucleotidesZIABC010852 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KLINMAN, DENNIS · 2009 to 2019
$11.3M
Spinal Neuroimmune Mechanisms Underlying IL-10 Gene Therapy for Pain ControlR01DA018156 · NIDA · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI MILLIGAN, ERIN DAMITA · 2004 to 2014
$3.3M
Pain facilitation via neuron-to-glia signalingR01DA017670 · NIDA · UNIVERSITY OF COLORADO AT BOULDER · PI WATKINS, LINDA · 2005 to 2009
$2.0M
Immune and Gilia Regulation of Pain & Analgesic ActionsK05DA024044 · NIDA · UNIVERSITY OF COLORADO · PI WATKINS, LINDA · 2008 to 2012
$616k
Immune/Glial Mediation of Exaggerated Pain StatesK02DA015642 · NIDA · UNIVERSITY OF COLORADO AT BOULDER · PI WATKINS, LINDA · 2003 to 2007
$600k
Pain control via spinal interleukin-10 gene therapyR21DA015656 · NIDA · UNIVERSITY OF COLORADO AT BOULDER · PI WATKINS, LINDA · 2002 to 2003
$296k
NHLBI NIH HHS HL5510NIDA NIH HHS DA015642NIDA NIH HHS DA015656NIDA NIH HHS DA018156NIDA NIH HHS K02 DA015642NIDA NIH HHS K05 DA024044NIDA NIH HHS R01 DA017670NIDA NIH HHS R01 DA018156NIDA NIH HHS R21 DA015656
6 · The paper itself

Abstract

We recently described a non-viral gene therapy paradigm offering long-term resolution of established neuropathic pain in several animal models. Here, the requirements for long-term therapeutic effects are described, and evidence is provided for a mechanism of action based on immunological priming of the intrathecal (i.t.) space. Long-term pain reversal was achieved when two i.t. injections of various naked plasmid DNA doses were separated by 5 h to 3 days. We show that an initial DNA injection, regardless of whether a transgene is included, leads to an accumulation of phagocytic innate immune cells. This accumulation coincides with the time in which subsequent DNA injection efficacy is potentiated. We show the ability of non-coding DNA to induce short-term pain reversal that is dependent on endogenous interleukin-10 (IL-10) signaling. Long-term efficacy requires the inclusion of an IL-10(F129S) transgene in the second injection. Blockade of IL-10, by a neutralizing antibody, either between the two injections or after the second injection induces therapeutic failure. These results show that this gene therapy paradigm uses an initial 'priming' injection of DNA to induce accumulation of phagocytic immune cells, allowing for potentiated efficacy of a subsequent 'therapeutic' DNA injection in a time- and dose-dependent manner.

Indexed as

Pain ManagementAnimalsDisease Models, AnimalDNAGenetic TherapyGenetic VectorsImmunity, InnateInjections, SpinalInterleukin-10MalePainPain ThresholdPlasmidsRatsRats, Sprague-DawleyDNAInterleukin-10

Identifiers

PMID19571887
PMCPMC2762489
OpenAlexW1966045089

What OpenQuestion holds

Textmetadata
LicenceTDM
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.