Evidence map›Paper›PMID 22509280›Full record

ArticlePloS one2012

Glucocorticoid-treated mice are an inappropriate positive control for long-term preclinical studies in the mdx mouse.

Arpana Sali, Alfredo D Guerron, Heather Gordish-Dressman, Christopher F Spurney, Micaela Iantorno, Eric P Hoffman, Kanneboyina Nagaraju

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03439670 (A Phase IIb Randomized, Double-blind, Parallel Group, Placebo- and Active-controlled Study With Double-Blind Extension to Assess the Efficacy and Safety of Vamorolone in Ambulant Boys With Duchenne Muscular Dystrophy), which is not on this map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.2field-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.

NCT03439670 phase2completednot on this mapstarted 2018, after this paper: background citation

A Phase IIb Randomized, Double-blind, Parallel Group, Placebo- and Active-controlled Study With Double-Blind Extension to Assess the Efficacy and Safety of Vamorolone in Ambulant Boys With Duchenne Muscular Dystrophy (DMD)

TypeinterventionalSponsorReveraGen BioPharma, Inc.Ran2018 to 2021Enrolled121ConditionsDuchenne Muscular DystrophyArmsVamorolone, Prednisone, Placebo
3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 79 citations in OpenAlex.

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  18. Observational
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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

7 authors at 2 institutions in 1 country.

Arpana SaliChildren's National Medical Center, Washington DC, United States of America.
Alfredo D Guerron
Heather Gordish-Dressman
Christopher F Spurney
Micaela Iantorno
Eric P Hoffman
Kanneboyina Nagaraju
Children's National · USGeorge Washington University · US

Funding

NCMRR-DC Core Molecular & Functional Outcome Measures in Rehabilitation MedicineR24HD050846 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI KNOBLACH, SUSAN M · 2005 to 2014
$8.6M
Wellstone Muscular Dystrophy Center: Children's Nat'l Med CtrU54HD053177 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI HOFFMAN, ERIC P. · 2005 to 2009
$7.3M
Pathogenesis of autoimmune myositis: Role of MHC Class 1R01AR050478 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI NAGARAJU, KANNEBOYINA · 2005 to 2009
$1.9M
Preclinical drug trial in mouse models of inflammationK26OD011171 · OD · STATE UNIVERSITY OF NY,BINGHAMTON · PI NAGARAJU, KANNEBOYINA · 2012 to 2015
$420k
Preclinical drug trial in mouse models of inflammationK26RR032082 · NCRR · CHILDREN'S RESEARCH INSTITUTE · PI NAGARAJU, KANNEBOYINA · 2011 to 2011
$106k
NCRR NIH HHS K26 RR032082NIAMS NIH HHS R01 AR050478NIAMS NIH HHS R01-AR050478NICHD NIH HHS 1U54HD053177-01A1NICHD NIH HHS 2R24HD050846-06NICHD NIH HHS R24 HD050846NICHD NIH HHS U54 HD053177NIH HHS K26 OD011171
6 · The paper itself

Abstract

backgroundDmd(mdx) (mdx) mice are used as a genetic and biochemical model of dystrophin deficiency. The long-term consequences of glucocorticoid (GC) treatment on dystrophin-deficient skeletal and heart muscle are not yet known. Here we used systematic phenotyping to assess the long-term consequences of GC treatment in mdx mice. Our investigation addressed not only the effects of GC on the disease phenotype but also the question of whether GCs can be used as a positive control for preclinical drug evaluations. METHODS AND

findingsWe performed nine pre-clinical efficacy trials (treated N = 129, untreated N = 106) of different durations in 9-to-50-week-old dystrophic mdx mice over a 3-year time period using standardized methods. In all these trials, we used either 1 mg/kg body weight of prednisone or 5 mg/kg body weight of prednisolone as positive controls to compare the efficacy of various test drugs. Data from untreated controls and GC-treated mice in the various trials have been pooled and analyzed to assess the effects of GCs on dystrophin-deficient skeletal and cardiac muscles of mdx mice. Our results indicate that continuous GC treatment results in early (e.g., at 50 days) improvements in normalized parameters such as grip strength, motor coordination and maximal in vitro force contractions on isolated EDL muscle, but these initial benefits are followed by a progressive loss of muscle strength after 100 days. We also found a significant increase in heart fibrosis that is reflected in a significant deterioration in cardiac systolic function after 100 days of treatment.

conclusionContinuous administration of prednisone to mdx mice initially improves skeletal muscle strength, but further therapy result in deterioration of muscle strength and cardiac function associated with enhanced cardiac fibrosis. These results suggest that GCs may not serve as an appropriate positive control for long-term mdx mouse preclinical trials.

Indexed as

AnimalsBehavior, AnimalBody WeightDrug Evaluation, PreclinicalDystrophinFemaleFibrosisGlucocorticoidsHand StrengthHeartMiceMice, Inbred mdxMotor ActivityMuscle ContractionMuscle, SkeletalMyocardiumDystrophinGlucocorticoids

Identifiers

PMID22509280
PMCPMC3317932
OpenAlexW2083119896

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.