Evidence map›Paper›PMID 33806803›Full record

ArticleInternational journal of molecular sciences2021

A Non-Toxic Concentration of Telomerase Inhibitor BIBR1532 Fails to Reduce

Virenkumar A Pandya, Hamish Crerar, Jamie S Mitchell, Rickie Patani

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 42% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Accelerated neuronal agingFrontiers in aging neuroscience · 2022
    Review
  6. Review
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

4 authors at 1 institution in 1 country.

Virenkumar A PandyaDepartment of Neuromuscular Diseases, University College London Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Hamish CrerarDepartment of Neuromuscular Diseases, University College London Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Jamie S MitchellDepartment of Neuromuscular Diseases, University College London Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Rickie PataniDepartment of Neuromuscular Diseases, University College London Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.ORCID 0000-0002-3825-7675
The Francis Crick Institute · GB

Funding

Medical Research Council MR/M02492X/1Medical Research Council MR/S006591/1
6 · The paper itself

Abstract

Several studies have shown that human induced pluripotent stem cell (iPSC)-derivatives are essentially fetal in terms of their maturational status. Inducing ageing in iPSC-motor neuron (MN) models of amyotrophic lateral sclerosis (ALS) has the potential to capture pathology with higher fidelity and consequently improve translational success. We show here that the telomerase inhibitor BIBR1532, hypothesised to recapitulate the telomere attrition hallmark of ageing in iPSC-MNs, was in fact cytotoxic to feeder-free iPSCs when used at doses previously shown to be effective in iPSCs grown on a layer of mouse embryonic fibroblasts. Toxicity in feeder-free cultures was not rescued by co-treatment with Rho Kinase (ROCK) inhibitor (Y-27632). Moreover, the highest concentration of BIBR1532 compatible with continued iPSC culture proved insufficient to induce detectable telomerase inhibition. Our data suggest that direct toxicity by BIBR1532 is the most likely cause of iPSC death observed, and that culture methods may influence enhanced toxicity. Therefore, recapitulation of ageing hallmarks in iPSC-MNs, which might reveal novel and relevant human disease targets in ALS, is not achievable in feeder-free culture through the use of this small molecule telomerase inhibitor.

Indexed as

AminobenzoatesCell DifferentiationCell LineEnzyme InhibitorsGene Expression RegulationHumansInduced Pluripotent Stem CellsMotor NeuronsNaphthalenesNeurogenesisTelomeraseAminobenzoatesBIBR 1532Enzyme InhibitorsNaphthalenesTelomeraseageingamyotrophic lateral sclerosis (ALS)BIBR1532induced pluripotent stem cells (iPSC)motor neurons (MNs)telomeraseTERT

Identifiers

PMID33806803
PMCPMC8005146
OpenAlexW3136407935

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.