Evidence map›Paper›PMID 24892251›Full record

ArticleVaccine2014

Physiologic and metabolic safety of butyrylcholinesterase gene therapy in mice.

Vishakantha Murthy, Yang Gao, Liyi Geng, Nathan K LeBrasseur, Thomas A White, Robin J Parks, Stephen Brimijoin

Abstract read
In one paragraph

Article in Vaccine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Drug addiction: a curable mental disorder?Acta pharmacologica Sinica · 2018
    Review
  6. Review
  7. Butyrylcholinesterase gene transfer in obese mice prevents postdieting body weight rebound by suppressing ghrelin signaling.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
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

7 authors at 3 institutions in 2 countries.

Vishakantha MurthyDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: Murthy.Vishakantha@mayo.edu.
Yang GaoDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA.
Liyi GengDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA.
Nathan K LeBrasseurRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
Thomas A WhiteRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA.
Robin J ParksOttawa Hospital Research Institute, Ottawa, Ontario, Canada.
Stephen BrimijoinDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA.
Mayo Clinic · USMayo Clinic in Florida · USOttawa Hospital · CA

Funding

Cocaine hydrolase gene therapy for cocaine abuse (DPI)DP1DA031340 · NIDA · MAYO CLINIC ROCHESTER · PI BRIMIJOIN, WILLIAM STEPHEN · 2010 to 2014
$3.9M
Development of a Human Hydrolase to Treat Cocaine Abuse and Overdose:Rat ModelsR01DA023979 · NIDA · MAYO CLINIC ROCHESTER · PI BRIMIJOIN, WILLIAM STEPHEN · 2007 to 2011
$2.3M
NIDA NIH HHS D1DA31340NIDA NIH HHS DP1 DA031340NIDA NIH HHS R01 DA023979NIDA NIH HHS R01DA23979
6 · The paper itself

Abstract

In continuing efforts to develop gene transfer of human butyrylcholinesterase (BChE) as therapy for cocaine addiction, we conducted wide-ranging studies of physiological and metabolic safety. For that purpose, mice were given injections of adeno-associated virus (AAV) vector or helper-dependent adenoviral (hdAD) vector encoding human or mouse BChE mutated for optimal cocaine hydrolysis. Age-matched controls received saline or AAV-luciferase control vector. At times when transduced BChE was abundant, physiologic and metabolic parameters in conscious animals were evaluated by non-invasive Echo-MRI and an automated "Comprehensive Laboratory Animal Monitoring System" (CLAMS). Despite high vector doses (up to 10(13) particles per mouse) and high levels of transgene protein in the plasma (∼1500-fold above baseline), the CLAMS apparatus revealed no adverse physiologic or metabolic effects. Likewise, body composition determined by Echo-MRI, and glucose tolerance remained normal. A CLAMS study of vector-treated mice given 40 mg/kg cocaine showed none of the physiologic and metabolic fluctuations exhibited in controls. We conclude that neither the tested vectors nor great excesses of circulating BChE affect general physiology directly, while they protect mice from disturbance by cocaine. Hence, viral gene transfer of BChE appears benign and worth exploring as a therapy for cocaine abuse and possibly other disorders as well.

Indexed as

Genetic TherapyAdenoviridaeAnimalsBasal MetabolismButyrylcholinesteraseCocaineCocaine-Related DisordersDependovirusEnergy MetabolismGenetic VectorsGlucose Tolerance TestHumansMaleMiceMice, Inbred BALB CMotor ActivityButyrylcholinesteraseCocaineAdeno-associated viral vectorButyrylcholinesteraseCocaine addictionGene therapyHelper-dependent adenoviral vectorOrganophosphate toxicity

Identifiers

PMID24892251
PMCPMC4077905
OpenAlexW1992087265

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.