Evidence map›Paper›PMID 31282429›Full record

ReviewJournal of neuromuscular diseases2019

Discovery of Novel Therapeutics for Muscular Dystrophies using Zebrafish Phenotypic Screens.

Jeffrey J Widrick, Genri Kawahara, Matthew S Alexander, Alan H Beggs, Louis M Kunkel

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of neuromuscular diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
–field-weighted citation impact
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

23 citing papers in PubMed.

  1. Review
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  13. PDE10A Inhibition Reduces the Manifestation of Pathology in DMD Zebrafish and Represses the Genetic Modifier PITPNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  14. Review
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  20. Catch a Tiny Fish by the Tail.Biophysical journal · 2020
    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

5 authors.

Jeffrey J WidrickDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Genri KawaharaDepartment of Pathophysiology, Tokyo Medical University, Tokyo, Japan.
Matthew S AlexanderDepartment of Pediatrics, Division of Neurology at the University of Alabama at Birmingham and Children's of Alabama; University of Alabama at Birmingham Center for Exercise Medicine; University of Alabama at Birmingham Civitan International Research Center; University of Alabama at Birmingham Department of Genetics; Birmingham, Alabama, USA.
Alan H BeggsDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Louis M KunkelDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Funding

Training Core [Parent Title: NOVEL THERAPEUTICS FOR FSHD]P50HD060848 · NICHD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI EMERSON, CHARLES P. · 2018 to 2023
$8.6M
SARCOMERIC PROTEINS IN NORMAL AND DISEASED MUSCLER01AR044345 · NIAMS · CHILDREN'S HOSPITAL BOSTON · PI BEGGS, ALAN H. · 1997 to 2017
$5.3M
Modulation of Jagged1/Pitpna in DMD as a means of therapyR01AR064300 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI KUNKEL, LOUIS M · 2014 to 2023
$3.9M
Genetic screening and therapies for nemaline myopathiesR01HD075802 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI BEGGS, ALAN H. · 2014 to 2018
$1.8M
NIAMS NIH HHS R01 AR044345NIAMS NIH HHS R01 AR064300NICHD NIH HHS P50 HD060848NICHD NIH HHS R01 HD075802
6 · The paper itself

Abstract

The recent availability and development of mutant and transgenic zebrafish strains that model human muscular dystrophies has created new research opportunities for therapeutic development. Not only do these models mimic many pathological aspects of human dystrophies, but their small size, large clutch sizes, rapid ex utero development, body transparency, and genetic tractability enable research approaches that would be inconceivable with mammalian model systems. Here we discuss the use of zebrafish models of muscular dystrophy to rapidly screen hundreds to thousands of bioactive compounds in order to identify novel therapeutic candidates that modulate pathologic phenotypes. We review the justification and rationale behind this unbiased approach, including how zebrafish screens have identified FDA-approved drugs that are candidates for treating Duchenne and limb girdle muscular dystrophies. Not only can these drugs be re-purposed for treating dystrophies in a fraction of the time and cost of new drug development, but their identification has revealed novel, unexpected directions for future therapy development. Phenotype-driven zebrafish drug screens are an important compliment to the more established mammalian, target-based approaches for rapidly developing and validating therapeutics for muscular dystrophies.

Indexed as

ZebrafishAnimalsDisease Models, AnimalDrug DiscoveryDrug Evaluation, PreclinicalMuscular DystrophiesMuscular Dystrophy, AnimalPhenotypeDanio rerioDrug discoverydrug screeningDuchenne muscular dystrophylimb-girdle muscular dystrophypreclinical drug evaluation

Identifiers

PMID31282429
PMCPMC6961982

What OpenQuestion holds

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LicenceCC BY-NC
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.