Evidence map›Paper›PMID 30831428›Full record

ArticleMolecular therapy. Nucleic acids2019

RNA-Based Therapy Utilizing Oculopharyngeal Muscular Dystrophy Transcript Knockdown and Replacement.

Aida Abu-Baker, Nawwaf Kharma, Jonathan Perreault, Alanna Grant, Masoud Shekarabi, Claudia Maios, Michele Dona, Christian Neri, Patrick A Dion, Alex Parker and 2 more

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 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.0field-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

9 citing papers in PubMed, 20 citations in OpenAlex.

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  8. Skeletal muscle in health and disease.Disease models & 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

12 authors at 8 institutions in 3 countries.

Aida Abu-BakerMontreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A2B4, Canada.
Nawwaf KharmaElectrical & Computer Engineering Department, Concordia University, 1455 boulevard de Maisonneuve O., Montreal, QC H3G 1M8, Canada; Biology Department, Concordia University, 7141 rue Sherbrooke O., Montreal, QC H4B 1R6, Canada.
Jonathan PerreaultINRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, QC H7V 1B7, Canada.
Alanna GrantMontreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A2B4, Canada.
Masoud ShekarabiDepartment of Neuroscience, Center for Neurobiology, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
Claudia MaiosCHUM Research Center, Montreal, QC H2X 3H8, Canada; Department of Neuroscience, University of Montreal, Montreal, QC H3T 1J4, Canada.
Michele DonaMontreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A2B4, Canada.
Christian NeriINSERM, Laboratory of Neuronal Cell Biology and Pathology, Center for Psychiatry and Neuroscience UMR 894 and University of Paris Descartes, Equipe d'accueil 4059, 75014 Paris, France.
Patrick A DionMontreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A2B4, Canada.
Alex ParkerCHUM Research Center, Montreal, QC H2X 3H8, Canada; Department of Neuroscience, University of Montreal, Montreal, QC H3T 1J4, Canada.
Luc VarinBiology Department, Concordia University, 7141 rue Sherbrooke O., Montreal, QC H4B 1R6, Canada.
Guy A RouleauMontreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A2B4, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada. Electronic address: guy.rouleau@mcgill.ca.
McGill University · CAConcordia University · CACentre Hospitalier de l’Université de Montréal · CAInstitut National de la Recherche Scientifique · CAMontreal Neurological Institute and Hospital · CATemple University · USUniversité de Montréal · CAUniversité Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Oculopharyngeal muscular dystrophy (OPMD) is caused by a small expansion of a short polyalanine (polyAla) tract in the poly(A)-binding protein nuclear 1 protein (PABPN1). Despite the monogenic nature of OPMD, no treatment is currently available. Here we report an RNA replacement strategy that has therapeutic potential in cell and C. elegans OPMD models. We develop selective microRNAs (miRNAs) against PABPN1, and we report that miRNAs and our previously developed hammerhead ribozymes (hhRzs) are capable of reducing the expression of both the mRNA and protein levels of PABPN1 by as much as 90%. Since OPMD derives from a very small expansion of GCG within the polyAla tract, our hhRz and miRNA molecules cannot distinguish between the wild-type and mutant mRNAs of PABPN1. Therefore, we designed an optimized-codon wild-type PABPN1 (opt-PABPN1) that is resistant to cleavage by hhRzs and miRNAs. Co-expression of opt-PABPN1 with either our hhRzs or miRNAs restored the level of PABPN1, concomitantly with a reduction in expanded PABPN1-associated cell death in a stable C2C12 OPMD model. Interestingly, knockdown of the PABPN1 by selective hhRzs in the C. elegans OPMD model significantly improved the motility of the PABPN1-13Ala worms. Taken together, RNA replacement therapy represents an exciting approach for OPMD treatment.

Indexed as

microRNAsOPMDPABPN1polyalanine disordersribozymesRNA replacement therapy

Identifiers

PMID30831428
PMCPMC6403420
OpenAlexW2911471940

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.