Evidence map›Paper›PMID 25004100›Full record

ArticleMolecular therapy. Nucleic acids2014

A short antisense oligonucleotide ameliorates symptoms of severe mouse models of spinal muscular atrophy.

Jeffrey M Keil, Joonbae Seo, Matthew D Howell, Walter H Hsu, Ravindra N Singh, Christine J DiDonato

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Nucleic acids, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 4 pooled it
–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

42 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Drug treatment for spinal muscular atrophy types II and III.The Cochrane database of systematic reviews · 2020
    Pooled it
  3. Drug treatment for spinal muscular atrophy type I.The Cochrane database of systematic reviews · 2019
    Pooled it
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  17. A survey of transcripts generated by spinal muscular atrophy genes.Biochimica et biophysica acta. Gene regulatory mechanisms · 2020
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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

6 authors.

Jeffrey M Keil1] Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Illinois, Chicago, Illinois, USA [2] Human Molecular Genetics Program, Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois, USA.
Joonbae SeoDepartment of Biomedical Sciences, Iowa State University, Ames, Iowa, USA.
Matthew D HowellDepartment of Biomedical Sciences, Iowa State University, Ames, Iowa, USA.
Walter H HsuDepartment of Biomedical Sciences, Iowa State University, Ames, Iowa, USA.
Ravindra N SinghDepartment of Biomedical Sciences, Iowa State University, Ames, Iowa, USA.
Christine J DiDonato1] Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Illinois, Chicago, Illinois, USA [2] Human Molecular Genetics Program, Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois, USA.

Funding

Splicing Regulation of Spinal Muscular Atrophy GenesR01NS055925 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SINGH, RAVINDRA N · 2006 to 2023
$5.6M
Spinal Muscular Atrophy: Inducing SMN Expression: Administrative SupplementR01NS060926 · NINDS · LURIE CHILDREN'S HOSPITAL OF CHICAGO · PI DIDONATO, CHRISTINE J. · 2007 to 2017
$3.4M
Small Oligonucleotides As Therapeutic Agents Of Spinal Muscular AtrophyR21NS072259 · NINDS · IOWA STATE UNIVERSITY · PI SINGH, RAVINDRA N · 2011 to 2012
$402k
NINDS NIH HHS R01 NS055925NINDS NIH HHS R01 NS060926NINDS NIH HHS R21 NS072259
6 · The paper itself

Abstract

Recent reports underscore the unparalleled potential of antisense-oligonucleotide (ASO)-based approaches to ameliorate various pathological conditions. However, in vivo studies validating the effectiveness of a short ASO (<10-mer) in the context of a human disease have not been performed. One disease with proven amenability to ASO-based therapy is spinal muscular atrophy (SMA). SMA is a neuromuscular disease caused by loss-of-function mutations in the survival motor neuron 1 (SMN1) gene. Correction of aberrant splicing of the remaining paralog, SMN2, can rescue mouse models of SMA. Here, we report the therapeutic efficacy of an 8-mer ASO (3UP8i) in two severe models of SMA. While 3UP8i modestly improved survival and function in the more severe Taiwanese SMA model, it dramatically increased survival, improved neuromuscular junction pathology, and tempered cardiac deficits in a new, less severe model of SMA. Our results expand the repertoire of ASO-based compounds for SMA therapy, and for the first time, demonstrate the in vivo efficacy of a short ASO in the context of a human disease.

Identifiers

PMID25004100
PMCPMC4121513

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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.