Evidence map›Paper›PMID 32302553›Full record

ArticleStem cell reports2020

Novel Drug Candidates Improve Ganglioside Accumulation and Neural Dysfunction in GM1 Gangliosidosis Models with Autophagy Activation.

Ryutaro Kajihara, Tadahiro Numakawa, Haruki Odaka, Yuji Yaginuma, Noemi Fusaki, Toshika Okumiya, Hirokazu Furuya, Seiji Inui, Takumi Era

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

Article in Stem cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

13 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
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  9. Emerging cellular themes in leukodystrophies.Frontiers in cell and developmental biology · 2022
    Review
  10. Inborn errors of metabolism: Lessons from iPSC models.Reviews in endocrine & metabolic disorders · 2021
    Review
  11. Review
  12. Article
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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

9 authors at 3 institutions in 1 country.

Ryutaro KajiharaDepartment of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan; Department of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0976, Japan.
Tadahiro NumakawaDepartment of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
Haruki OdakaDepartment of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
Yuji YaginumaDepartment of Morphological and Physiological Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0976, Japan.
Noemi FusakiUniversity Research Administration Center, Office of Research Promotion, Tohoku University, Tohoku 980-8577, Japan.
Toshika OkumiyaDepartment of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0976, Japan.
Hirokazu FuruyaDepartment of Neurology, Kochi Medical School, Kochi University, Kochi 783-8505, Japan.
Seiji InuiDepartment of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0976, Japan.
Takumi EraDepartment of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan. Electronic address: tera@kumamoto-u.ac.jp.
Kumamoto University · JPKōchi University · JPTohoku University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

GM1 gangliosidosis is a lysosomal storage disease caused by loss of lysosomal β-galactosidase activity and characterized by progressive neurodegeneration due to massive accumulation of GM1 ganglioside in the brain. Here, we generated induced pluripotent stem cells (iPSCs) derived from patients with GM1 gangliosidosis, and the resultant neurons showed impaired neurotransmitter release as a presynaptic function and accumulation of GM1 ganglioside. Treatment of normal neurons with GM1 ganglioside also disturbed presynaptic function. A high-content drug-screening system was then established and identified two compounds as drug candidates for GM1 gangliosidosis. Treatment of the patient-derived neurons with the candidate agents activated autophagy pathways, reducing GM1 ganglioside accumulation in vitro and in vivo, and restoring the presynaptic dysfunction. Our findings thus demonstrated the potential value of patient-derived iPSC lines as cellular models of GM1 gangliosidosis and revealed two potential therapeutic agents for future clinical application.

Indexed as

AutophagyCells, CulturedDrug DevelopmentGangliosidosis, GM1G(M1) GangliosideHumansInduced Pluripotent Stem CellsNeuronsNeuroprotective AgentsSynapsesG(M1) GangliosideNeuroprotective Agentsdrug developmentGM1 gangliosidosisinduced pluripotent stem cellslysosomal storage disease

Identifiers

PMID32302553
PMCPMC7220856
OpenAlexW3016504524

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.