Evidence map›Paper›PMID 31678734›Full record

ArticleMolecular therapy. Nucleic acids2019

Targeting RyR Activity Boosts Antisense Exon 44 and 45 Skipping in Human DMD Skeletal or Cardiac Muscle Culture Models.

Florian Barthélémy, Richard T Wang, Christopher Hsu, Emilie D Douine, Eugene E Marcantonio, 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, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

16 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
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  7. Current Strategies of Muscular Dystrophy Therapeutics: An Overview.Methods in molecular biology (Clifton, N.J.) · 2023
    Review
  8. Article
  9. MicroRNAs in Dystrophinopathy.International journal of molecular sciences · 2022
    Review
  10. 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

7 authors at 3 institutions in 1 country.

Florian BarthélémyDepartment 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; Center for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA, USA.
Richard T WangCenter 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.
Christopher HsuDepartment 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; Center for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA, USA.
Emilie D DouineCenter 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.
Eugene E MarcantonioARMGO Pharma, Inc., Ardsley, NY 10502, 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; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, 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 MiceliDepartment 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; Center for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA, USA; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, 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. Electronic address: cmiceli@ucla.edu.
University of California, Los Angeles · USBroad Center · USARMGO Pharma (United States) · US

Funding

Training and education CoreU54AR052646 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI MCNALLY, ELIZABETH M, SWEENEY, H LEE · 2005 to 2020
$24.1M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
UCLA Muscular Dystrophy Core CenterP30AR057230 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SPENCER, MELISSA JAN · 2009 to 2018
$6.2M
NIAMS NIH HHS P30 AR057230NIAMS NIH HHS U54 AR052646NIDDK NIH HHS P30 DK041301
6 · The paper itself

Abstract

Systemic delivery of antisense oligonucleotides (AO) for DMD exon skipping has proven effective for reframing DMD mRNA, rescuing dystrophin expression, and slowing disease progression in animal models. In humans with Duchenne muscular dystrophy treated with AOs, low levels of dystrophin have been induced, and modest slowing of disease progression has been observed, highlighting the need for improved efficiency of human skipping drugs. Here, we demonstrate that dantrolene and Rycals S107 and ARM210 potentiate AO-mediated exon skipping of exon 44 or exon 45 in patient-derived myotube cultures with appropriate mutations. Further, dantrolene is shown to boost AO-mediated exon skipping in patient-derived, induced cardiomyocyte cultures. Our findings further validate the ryanodine receptors (RyR) as the likely target responsible for exon skip boosting and demonstrate potential applicability beyond exon 51 skipping. These data provide preclinical support of dantrolene trial as an adjuvant to AO-mediated exon-skipping therapy in humans and identify a novel Rycal, ARM210, for development as a potential exon-skipping booster. Further, they highlight the value of mutation-specific DMD culture models for basic discovery, preclinical drug screening and translation of personalized genetic medicines.

Indexed as

ARM210armgocombination therapydantroleneDuchenne muscular dystrophydystrophinexon skippingmuscletherapy

Identifiers

PMID31678734
PMCPMC6838898
OpenAlexW2975472616

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.