Evidence map›Paper›PMID 37365234›Full record

ArticleScientific reports2023

Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.

Casey J Lumpkin, Ashlee W Harris, Andrew J Connell, Ryan W Kirk, Joshua A Whiting, Luciano Saieva, Livio Pellizzoni, Arthur H M Burghes, Matthew E R Butchbach

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

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. 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

9 authors at 5 institutions in 1 country.

Casey J Lumpkin *Division of Neurology, Nemours Children's Hospital Delaware, 4462 E400 DuPont Experimental Station, 200 Powder Mill Road, Wilmington, DE, 19803, USA.
Ashlee W Harris *Division of Neurology, Nemours Children's Hospital Delaware, 4462 E400 DuPont Experimental Station, 200 Powder Mill Road, Wilmington, DE, 19803, USA.
Andrew J Connell *Division of Neurology, Nemours Children's Hospital Delaware, 4462 E400 DuPont Experimental Station, 200 Powder Mill Road, Wilmington, DE, 19803, USA.
Ryan W KirkDivision of Neurology, Nemours Children's Hospital Delaware, 4462 E400 DuPont Experimental Station, 200 Powder Mill Road, Wilmington, DE, 19803, USA.
Joshua A WhitingDivision of Neurology, Nemours Children's Hospital Delaware, 4462 E400 DuPont Experimental Station, 200 Powder Mill Road, Wilmington, DE, 19803, USA.
Luciano SaievaDepartment of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Livio PellizzoniDepartment of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Arthur H M BurghesDepartment of Biological Chemistry and Pharmacology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Matthew E R ButchbachDivision of Neurology, Nemours Children's Hospital Delaware, 4462 E400 DuPont Experimental Station, 200 Powder Mill Road, Wilmington, DE, 19803, USA. Matthew.Butchbach@nemours.org.
Experimental Station · USColumbia University · USDuPont (United States) · USThe Ohio State University Wexner Medical Center · USThomas Jefferson University · US

Funding

Center for Pediatric ResearchP20GM103464 · NIGMS · NEMOURS CHILDREN'S HOSPITAL, DELAWARE · PI SHAFFER, THOMAS H · 2012 to 2014
$5.6M
Center for Pediatric Research Pilot ProgramP30GM114736 · NIGMS · NEMOURS CHILDREN'S HOSPITAL, DELAWARE · PI SHAFFER, THOMAS H · 2015 to 2019
$5.1M
RNA-Mediated Mechanisms of Motor System Dysfunction in Spinal Muscular AtrophyR01NS102451 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Livio Pellizzoni · 2017 to 2026
$3.9M
SURVIVAL MOTOR NEURON GENES IN SPINAL MUSCULAR ATROPHYR01NS038650 · NINDS · OHIO STATE UNIVERSITY · PI BURGHES, ARTHUR H. M. · 1999 to 2011
$3.8M
Integrated Genome Browser and IGB AppsR01GM103463 · NIGMS · UNIVERSITY OF NORTH CAROLINA CHARLOTTE · PI LORAINE, ANN E · 2012 to 2019
$2.7M
NIGMS NIH HHS P20 GM103464NIGMS NIH HHS P30 GM114736NIGMS NIH HHS R01 GM103463NIH HHS P20GM103463NIH HHS R01NS102451NIH HHS R01NS38650NINDS NIH HHS R01 NS038650NINDS NIH HHS R01 NS102451
6 · The paper itself

Abstract

Proximal spinal muscular atrophy (SMA) is a leading genetic cause for infant death in the world and results from the selective loss of motor neurons in the spinal cord. SMA is a consequence of low levels of SMN protein and small molecules that can increase SMN expression are of considerable interest as potential therapeutics. Previous studies have shown that both 4-phenylbutyrate (4PBA) and trichostatin A (TSA) increase SMN expression in dermal fibroblasts derived from SMA patients. AR42 is a 4PBA-tethered TSA derivative that is a very potent histone deacetylase inhibitor. SMA patient fibroblasts were treated with either AR42, AR19 (a related analogue), 4PBA, TSA or vehicle for 5 days and then immunostained for SMN localization. AR42 as well as 4PBA and TSA increased the number of SMN-positive nuclear gems in a dose-dependent manner while AR19 did not show marked changes in gem numbers. While gem number was increased in AR42-treated SMA fibroblasts, there were no significant changes in FL-SMN mRNA or SMN protein. The neuroprotective effect of this compound was then assessed in SMNΔ7 SMA (SMN2

Indexed as

Muscular Atrophy, SpinalProto-Oncogene Proteins c-aktAnimalsDisease Models, AnimalHistone Deacetylase InhibitorsHydroxamic AcidsMiceMotor NeuronsPhenylbutyratesSurvival of Motor Neuron 1 Protein4-phenylbutyric acidHistone Deacetylase InhibitorsHydroxamic AcidsPhenylbutyratesProto-Oncogene Proteins c-aktSurvival of Motor Neuron 1 Proteintrichostatin A

Identifiers

PMID37365234
PMCPMC10293174
OpenAlexW4382138610

What OpenQuestion holds

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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.