Evidence map›Paper›PMID 31374463›Full record

ArticleStem cell research2019

Antisense oligonucleotide therapy rescues aggresome formation in a novel spinocerebellar ataxia type 3 human embryonic stem cell line.

Lauren R Moore, Laura Keller, David D Bushart, Rodrigo G Delatorre, Duojia Li, Hayley S McLoughlin, Maria do Carmo Costa, Vikram G Shakkottai, Gary D Smith, Henry L Paulson

Open access · goldAbstract read
In one paragraph

Article in Stem cell research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

25 citing papers in PubMed, 43 citations in OpenAlex.

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  16. Suppression of Kv3.3 channels by antisense oligonucleotides reverses biochemical effects and motor impairment in spinocerebellar ataxia type 13 mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
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  18. Identification of the Prodromal Symptoms and Pre-Ataxic Stage in Cerebellar Disorders: The Next Challenge.International journal of environmental research and public health · 2021
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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

10 authors at 2 institutions in 1 country.

Lauren R MooreDepartment of Neurology, 109 Zina Pitcher Place, University of Michigan, Ann Arbor, MI 48109, United States; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, United States.
Laura KellerMStem Cell Laboratories, University of Michigan, Ann Arbor, MI 48109, United States.
David D BushartDepartment of Neurology, 109 Zina Pitcher Place, University of Michigan, Ann Arbor, MI 48109, United States.
Rodrigo G DelatorreDepartment of Neurology, 109 Zina Pitcher Place, University of Michigan, Ann Arbor, MI 48109, United States.
Duojia LiDepartment of Neurology, 109 Zina Pitcher Place, University of Michigan, Ann Arbor, MI 48109, United States.
Hayley S McLoughlinDepartment of Neurology, 109 Zina Pitcher Place, University of Michigan, Ann Arbor, MI 48109, United States.
Maria do Carmo CostaDepartment of Neurology, 109 Zina Pitcher Place, University of Michigan, Ann Arbor, MI 48109, United States.
Vikram G ShakkottaiDepartment of Neurology, 109 Zina Pitcher Place, University of Michigan, Ann Arbor, MI 48109, United States.
Gary D SmithMStem Cell Laboratories, University of Michigan, Ann Arbor, MI 48109, United States; Departments of Ob/Gyn, Physiology, Urology, University of Michigan, Ann Arbor, MI 48109, United States.
Henry L PaulsonDepartment of Neurology, 109 Zina Pitcher Place, University of Michigan, Ann Arbor, MI 48109, United States. Electronic address: henryp@med.umich.edu.
University of Michigan–Ann Arbor · USMichigan Medicine · US

Funding

Mechanisms of Polyglutamine NeurodegenerationR01NS038712 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PAULSON, HENRY L · 2000 to 2019
$8.1M
Identifying symptomatic and neuroprotective strategies for cerebellar ataxiaR01NS085054 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI SHAKKOTTAI, VIKRAM GOVINDARAJU · 2013 to 2023
$4.3M
NINDS NIH HHS R01 NS038712
6 · The paper itself

Abstract

Spinocerebellar ataxia type 3 (SCA3) is a fatal, late-onset neurodegenerative disorder characterized by selective neuropathology in the brainstem, cerebellum, spinal cord, and substantia nigra. Here we report the first NIH-approved human embryonic stem cell (hESC) line derived from an embryo harboring the SCA3 mutation. Referred to as SCA3-hESC, this line is heterozygous for the mutant polyglutamine-encoding CAG repeat expansion in the ATXN3 gene. We observed relevant molecular hallmarks of the human disease at all differentiation stages from stem cells to cortical neurons, including robust ATXN3 aggregation and altered expression of key components of the protein quality control machinery. In addition, SCA3-hESCs exhibit nuclear accumulation of mutant ATXN3 and form p62-positive aggresomes. Finally, antisense oligonucleotide-mediated reduction of ATXN3 markedly suppressed aggresome formation. The SCA3-hESC line offers a unique and highly relevant human disease model that holds strong potential to advance understanding of SCA3 disease mechanisms and facilitate the evaluation of candidate therapies for SCA3.

Indexed as

Ataxin-3Cells, CulturedElectrophysiologyHuman Embryonic Stem CellsHumansImmunoblottingImmunohistochemistryMachado-Joseph DiseaseMaleOligonucleotides, AntisenseAtaxin-3Oligonucleotides, AntisenseAggresomeAntisense oligonucleotideAtaxin-3Machado-Joseph diseaseNeurodegenerationPolyglutamine disease

Identifiers

PMID31374463
PMCPMC6736695
OpenAlexW2961853070

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.