Evidence map›Paper›PMID 29858053›Full record

ArticleMolecular therapy. Nucleic acids2018

Repurposing Dantrolene for Long-Term Combination Therapy to Potentiate Antisense-Mediated DMD Exon Skipping in the mdx Mouse.

Derek W Wang, Ekaterina I Mokhonova, Genevieve C Kendall, Diana Becerra, Yalda B Naeini, Rita M Cantor, Melissa J Spencer, Stanley F Nelson, M Carrie Miceli

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Nucleic acids, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.5field-weighted citation impact, top 38% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Current Strategies of Muscular Dystrophy Therapeutics: An Overview.Methods in molecular biology (Clifton, N.J.) · 2023
    Review
  4. Article
  5. Article
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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

9 authors at 1 institution in 1 country.

Derek W WangCenter for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA, USA; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine and College of Letters and Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
Ekaterina I MokhonovaCenter for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA, USA; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine and College of Letters and Sciences, University of California, Los Angeles, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Genevieve C KendallCenter for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Diana BecerraCenter for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Yalda B NaeiniDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Rita M CantorDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Melissa J SpencerCenter for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Stanley F NelsonCenter for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
M Carrie MiceliCenter for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA, USA; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine and College of Letters and Sciences, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: cmiceli@ucla.edu.
University of California, Los Angeles · US

Funding

UCLA Muscular Dystrophy Core CenterP30AR057230 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SPENCER, MELISSA JAN · 2009 to 2018
$6.2M
Muscle Cell Biology, Pathophysiology, and TherapeuticsT32AR065972 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Rachelle Hope Crosbie, THOMAS A. RANDO · 2016 to 2026
$3.9M
NIAMS NIH HHS P30 AR057230NIAMS NIH HHS T32 AR065972
6 · The paper itself

Abstract

Duchenne muscular dystrophy (DMD) is caused by mutations in DMD, resulting in loss of dystrophin, which is essential to muscle health. DMD "exon skipping" uses anti-sense oligo-nucleotides (AONs) to force specific exon exclusion during mRNA processing to restore reading frame and rescue of partially functional dystrophin protein. Although exon-skipping drugs in humans show promise, levels of rescued dystrophin protein remain suboptimal. We previously identified dantrolene as a skip booster when combined with AON in human DMD cultures and short-term mdx dystrophic mouse studies. Here, we assess the effect of dantrolene/AON combination on DMD exon-23 skipping over long-term mdx treatment under conditions that better approximate potential human dosing. To evaluate the dantrolene/AON combination treatment effect on dystrophin induction, we assayed three AON doses, with and without oral dantrolene, to assess multiple outcomes across different muscles. Meta-analyses of the results of statistical tests from both the quadriceps and diaphragm assessing contributions of dantrolene beyond AON, across all AON treatment groups, provide strong evidence that dantrolene modestly boosts exon skipping and dystrophin rescue while reducing muscle pathology in mdx mice (p < 0.0087). These findings support a trial of combination dantrolene/AON to increase exon-skipping efficacy and highlight the value of combinatorial approaches and Food and Drug Administration (FDA) drug re-purposing for discovery of unsuspected therapeutic application and rapid translation.

Indexed as

combination therapydantroleneDuchenne muscular dystrophydystrophinexon skipping

Identifiers

PMID29858053
PMCPMC5992346
OpenAlexW2790974276

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.