Evidence map›Paper›PMID 24085526›Full record

ArticleJournal of molecular neuroscience : MN2014

Preclinical studies on neurobehavioral and neuromuscular effects of cocaine hydrolase gene therapy in mice.

Vishakantha Murthy, Yang Gao, Liyi Geng, Nathan LeBrasseur, Thomas White, Stephen Brimijoin

Abstract read
In one paragraph

Article in Journal of molecular neuroscience : MN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
4.4field-weighted citation impact, top 7% 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

14 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Plasma butyrylcholinesterase regulates ghrelin to control aggression.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  12. Journal of molecular neuroscience: impacting our brains.Journal of molecular neuroscience : MN · 2014
    Article
  13. Article
  14. Long-term reduction of cocaine self-administration in rats treated with adenoviral vector-delivered cocaine hydrolase: evidence for enzymatic activity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014
    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

6 authors at 2 institutions in 1 country.

Vishakantha MurthyMayo Clinic, Rochester, MN, USA.
Yang Gao
Liyi Geng
Nathan LeBrasseur
Thomas White
Stephen Brimijoin
Mayo Clinic in Arizona · USMayo Clinic in Florida · US

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 DP1 DA031340NIDA NIH HHS DP1DA31340NIDA NIH HHS R01 DA023979NIDA NIH HHS R01DA23979
6 · The paper itself

Abstract

Cocaine hydrolase gene transfer of mutated human butyrylcholinesterase (BChE) is evolving as a promising therapy for cocaine addiction. BChE levels after gene transfer can be 1,500-fold above those in untreated mice, making this enzyme the second most abundant plasma protein. Because mutated BChE is approximately 70 % as efficient in hydrolyzing acetylcholine as wild-type enzyme, it is important to examine the impact on cholinergic function. Here, we focused on memory and cognition (Stone T-maze), basic neuromuscular function (treadmill endurance and grip strength), and coordination (Rotarod). BALB/c mice were given adeno-associated virus vector or helper-dependent adenoviral vector encoding mouse or human BChE optimized for cocaine. Age-matched controls received saline or luciferase vector. Despite high doses (up to 10(13) particles per mouse) and high transgene expression (1,000-fold above baseline), no deleterious effects of vector treatment were seen in neurobehavioral functions. The vector-treated mice performed as saline-treated and luciferase controls in maze studies and strength tests, and their Rotarod and treadmill performance decreased less with age. Thus, neither the viral vectors nor the large excess of BChE caused observable toxic effects on the motor and cognitive systems investigated. This outcome justifies further steps toward an eventual clinical trial of vector-based gene transfer for cocaine abuse.

Indexed as

Genetic TherapyHand StrengthMaze LearningAnimalsButyrylcholinesteraseCocaineCocaine-Related DisordersDependovirusHumansMaleMiceMice, Inbred BALB CPsychomotor PerformanceButyrylcholinesteraseCocaine

Identifiers

PMID24085526
PMCPMC3983183
OpenAlexW1993795668

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.