ArticleScience translational medicine2019
Human genetics and neuropathology suggest a link between miR-218 and amyotrophic lateral sclerosis pathophysiology.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04840823 (A Randomized, Double-blind, Parallel Group, Single Centre, Phase 1b/2 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Three Orally Administered Doses of Enoxacin), which is not on this map. Cited by 35 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 6% of its field
What it found
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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.
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.
NCT04840823 phase1 / phase2completednot on this mapstarted 2021, after this paper: background citation
A Randomized, Double-blind, Parallel Group, Single Centre, Phase 1b/2 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Three Orally Administered Doses of Enoxacin (200mg Twice Daily, 400mg Twice Daily and 600mg Twice Daily) in Adults With Amyotrophic Lateral Sclerosis
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
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Corrections and comments
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Authors and funding
45 authors at 17 institutions in 8 countries.
Irit ReichensteinDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.ORCID 0000-0003-0073-9182
Chen EitanDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.ORCID 0000-0001-6952-0336
Sandra Diaz-GarciaDepartment of Neurosciences, UC San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-4536-0523
Guy HaimDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Iddo MagenDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.ORCID 0000-0002-3011-3175
Aviad SianyDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.ORCID 0000-0003-1689-8698
Mariah L HoyeDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0002-3430-2782
Natali RivkinDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Tsviya OlenderDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.ORCID 0000-0002-4194-6420
Beata TothDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.ORCID 0000-0002-6124-3028
Revital RavidDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.ORCID 0000-0002-1309-7142
Amitai D MandelbaumDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.ORCID 0000-0001-6860-8491
Eran YanowskiDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.ORCID 0000-0002-0234-7476
Jing LiangDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.ORCID 0000-0003-0480-0390
Jeffrey K RymerDivision of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.ORCID 0000-0003-3630-069X
Rivka LevyDepartment of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel.ORCID 0000-0002-3781-2593
Gilad BeckStem Cell Core and Advanced Cell Technologies Unit, Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 7610001, Israel.ORCID 0000-0003-4290-1360
Elena AinbinderStem Cell Core and Advanced Cell Technologies Unit, Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 7610001, Israel.ORCID 0000-0003-4747-445X
Sali M K FarhanAnalytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0001-5936-0957
Kimberly A LennoxIntegrated DNA Technologies, 1710 Commercial Park, Coralville, IA 52241, USA.ORCID 0000-0002-5084-3482
Nicole M BodeIntegrated DNA Technologies, 1710 Commercial Park, Coralville, IA 52241, USA.ORCID 0000-0001-7209-303X
Mark A BehlkeIntegrated DNA Technologies, 1710 Commercial Park, Coralville, IA 52241, USA.ORCID 0000-0002-4218-857X
Thomas MöllerDepartment of Neurology, School of Medicine, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0003-3671-5684
Smita SaxenaDepartment of Neurology, Inselspital University Hospital, University of Bern, Freiburgstrasse 16, CH-3010 Bern, Bern, Switzerland.ORCID 0000-0003-4574-4591
Cristiane A M MorenoDepartment of Neurology, Columbia University, New York, NY 10032, USA.ORCID 0000-0002-5867-6359
Giancarlo CostagutaGene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Kristel R van EijkProject MinE ALS Sequencing Consortium.
Hemali PhatnaniCenter for Genomics of Neurodegenerative Disease (CGND) and New York Genome Center (NYGC) ALS Consortium, New York, NY 10013, USA.ORCID 0000-0002-6571-3891
Ammar Al-ChalabiProject MinE ALS Sequencing Consortium.ORCID 0000-0002-4924-7712
A Nazli BaşakProject MinE ALS Sequencing Consortium.
Leonard H van den BergProject MinE ALS Sequencing Consortium.ORCID 0000-0002-6559-3965
Orla HardimanProject MinE ALS Sequencing Consortium.ORCID 0000-0003-2610-1291
John E LandersProject MinE ALS Sequencing Consortium.ORCID 0000-0001-8084-5043
Jesus S MoraProject MinE ALS Sequencing Consortium.ORCID 0000-0001-6633-5354
Karen E MorrisonProject MinE ALS Sequencing Consortium.ORCID 0000-0003-0216-5717
Pamela J ShawProject MinE ALS Sequencing Consortium.ORCID 0000-0002-8925-2567
Jan H VeldinkProject MinE ALS Sequencing Consortium.ORCID 0000-0001-5572-9657
Samuel L PfaffGene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.ORCID 0000-0002-2142-166X
Ofer YizharDepartment of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Christina GrossDivision of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.ORCID 0000-0001-6057-2527
Robert H BrownDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
John M RavitsDepartment of Neurosciences, UC San Diego, La Jolla, CA 92093, USA.ORCID 0000-0001-6521-4649
Matthew B HarmsDepartment of Neurology, Columbia University, New York, NY 10032, USA.ORCID 0000-0002-3395-1633
Timothy M MillerDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0002-3424-5511
Eran HornsteinDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel. eran.hornstein@weizmann.ac.il.ORCID 0000-0002-5534-1924
Weizmann Institute of Science · ILNew Mexico Consortium · USIntegrated DNA Technologies (United States) · USUniversity Medical Center Utrecht · NLCincinnati Children's Hospital Medical Center · USColumbia University · USSalk Institute for Biological Studies · USUniversity of California San Diego · USUniversity of Massachusetts Chan Medical School · USWashington University in St. Louis · USBroad Institute · USKing's College London · GBKoç University · TRNew York Genome Center · USTrinity College Dublin · IEUniversity of Bern · CHUniversity of Washington · US
Funding
Expanding the chemical diversity of therapeutic oligonucleotides to treat neurodegenerative disordersR01NS104022 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ANASTASIA KHVOROVA · 2017 to 2026
$6.0MNext-generation antisense therapeutics for ALS and frontotemporal dementiaR01NS111990 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Robert H Brown, Jonathan K Watts · 2019 to 2026
$5.2MIdentification of genes causative for familial ALS gene using exome sequencingR01NS073873 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LANDERS, JOHN E · 2011 to 2019
$4.6MUsing motor neuron specific miRNA to understand and develop novel therapeutics for motor neuron diseaseR01NS078398 · NINDS · WASHINGTON UNIVERSITY · PI MILLER, TIMOTHY M. · 2012 to 2021
$3.9MMicroRNA-mediated silencing of the Kv4.2 complex in epilepsyR01NS092705 · NINDS · CINCINNATI CHILDRENS HOSP MED CTR · PI GROSS, CHRISTINA · 2016 to 2020
$1.8MIdentification and Characterization of ALS/FTD Associated Variants Using Whole Genome SequencingR56NS073873 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LANDERS, JOHN E · 2020 to 2020
$586kDefining Motor Neuron-Specific miRNAs in ALSF31NS092340 · NINDS · WASHINGTON UNIVERSITY · PI HOYE, MARIAH LAWLER · 2015 to 2017
$90kMedical Research Council G0600974Medical Research Council MR/L501529/1Medical Research Council MR/R024804/1Motor Neurone Disease Association TURNER/OCT15/972-797NINDS NIH HHS F31 NS092340NINDS NIH HHS R01 NS073873NINDS NIH HHS R01 NS078398NINDS NIH HHS R01 NS092705NINDS NIH HHS R01 NS104022NINDS NIH HHS R01 NS111990NINDS NIH HHS R56 NS073873Wellcome Trust
Abstract
Motor neuron-specific microRNA-218 (miR-218) has recently received attention because of its roles in mouse development. However, miR-218 relevance to human motor neuron disease was not yet explored. Here, we demonstrate by neuropathology that miR-218 is abundant in healthy human motor neurons. However, in amyotrophic lateral sclerosis (ALS) motor neurons, miR-218 is down-regulated and its mRNA targets are reciprocally up-regulated (derepressed). We further identify the potassium channel
Indexed as
Amyotrophic Lateral SclerosisAnimalsEther-A-Go-Go Potassium ChannelsHumansMiceMicroRNAsMotor NeuronsNeuronsNeuropathologyEther-A-Go-Go Potassium ChannelsKCNH1 protein, humanMicroRNAsMIRN218 microRNA, human
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Registered trials
NCT04840823ClinicalTrials.gov
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.