Evidence map›Paper›PMID 28017471›Full record

ArticleNeuron2017

The Antisense Transcript SMN-AS1 Regulates SMN Expression and Is a Novel Therapeutic Target for Spinal Muscular Atrophy.

Constantin d'Ydewalle, Daniel M Ramos, Noah J Pyles, Shi-Yan Ng, Mariusz Gorz, Celeste M Pilato, Karen Ling, Lingling Kong, Amanda J Ward, Lee L Rubin and 3 more

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

Article in Neuron, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 3 pooled it
8.3field-weighted citation impact, top 2% 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

98 citing papers in PubMed, 3 syntheses or guidelines pooled it, 134 citations in OpenAlex.

  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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  5. Trial
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  16. Article
  17. Patient-specific responses toMolecular therapy. Methods & clinical development · 2024
    Article
  18. In Search of Spinal Muscular Atrophy Disease Modifiers.International journal of molecular sciences · 2024
    Review
  19. Article
  20. Review

38 more citing papers are in PubMed but not listed here.

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

13 authors at 6 institutions in 1 country.

Constantin d'YdewalleDepartment of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Daniel M RamosDepartment of Neuroscience, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Noah J PylesDepartment of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Shi-Yan NgDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Mariusz GorzDepartment of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Celeste M PilatoDepartment of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Karen LingIonis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA 92010, USA.
Lingling KongDepartment of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Amanda J WardKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02142, USA.
Lee L RubinDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Frank RigoIonis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA 92010, USA.
C Frank BennettIonis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA 92010, USA.
Charlotte J SumnerDepartment of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA. Electronic address: csumner1@jhmi.edu.
Johns Hopkins University · USIonis Pharmaceuticals (United States) · USJohns Hopkins Medicine · USHarvard Stem Cell Institute · USHarvard University · USMassachusetts Institute of Technology · US

Funding

Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Targeting a SMN lncRNA for the treatment of SMAR01NS096770 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SUMNER, CHARLOTTE JANE · 2016 to 2020
$2.2M
NCATS NIH HHS UL1 TR001079NINDS NIH HHS R01 NS096770
6 · The paper itself

Abstract

The neuromuscular disorder spinal muscular atrophy (SMA), the most common inherited killer of infants, is caused by insufficient expression of survival motor neuron (SMN) protein. SMA therapeutics development efforts have focused on identifying strategies to increase SMN expression. We identified a long non-coding RNA (lncRNA) that arises from the antisense strand of SMN, SMN-AS1, which is enriched in neurons and transcriptionally represses SMN expression by recruiting the epigenetic Polycomb repressive complex-2. Targeted degradation of SMN-AS1 with antisense oligonucleotides (ASOs) increases SMN expression in patient-derived cells, cultured neurons, and the mouse central nervous system. SMN-AS1 ASOs delivered together with SMN2 splice-switching oligonucleotides additively increase SMN expression and improve survival of severe SMA mice. This study is the first proof of concept that targeting a lncRNA to transcriptionally activate SMN2 can be combined with SMN2 splicing modification to ameliorate SMA and demonstrates the promise of combinatorial ASOs for the treatment of neurogenetic disorders.

Indexed as

Gene Expression RegulationAnimalsBlotting, WesternCells, CulturedCerebral CortexChromatin ImmunoprecipitationDisease Models, AnimalHumansInduced Pluripotent Stem CellsMiceMotor NeuronsMuscular Atrophy, SpinalNeuronsOligonucleotides, AntisensePolycomb Repressive Complex 2Promoter Regions, GeneticOligonucleotides, AntisensePolycomb Repressive Complex 2RNA, AntisenseRNA, Long NoncodingSmn1 protein, mouseSMN2 protein, mouseSurvival of Motor Neuron 1 ProteinSurvival of Motor Neuron 2 Proteinantisense oligonucleotideslong non-coding RNASMA therapeuticsSMNspinal muscular atrophy

Identifiers

PMID28017471
PMCPMC5223741
OpenAlexW2562013491

What OpenQuestion holds

Textmetadata
LicenceTDM
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.