Evidence map›Paper›PMID 40541176›Full record

ArticleStem cell reports2025

Telmisartan is neuroprotective in a hiPSC-derived spinal microtissue model for C9orf72 ALS via inhibition of neuroinflammation.

Berkiye Sonustun, Björn F Vahsen, Mario Ledesma-Terrón, Zhuoning Li, Laura Tuffery, Nan Xu, Elizabeth L Calder, Johannes Jungverdorben, Leslie Weber, Aaron Zhong and 5 more

Abstract read
In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
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

15 authors.

Berkiye SonustunDevelopmental Biology Program & Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA.
Björn F VahsenOxford Motor Neuron Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK.
Mario Ledesma-TerrónCentro de Biologia Molecular Severo Ochoa, Departamento de Fisica de la Materia Condensada, Instituto Nicolas Cabrera, and Condensed Matter Physics Center (IFIMAC), Universidad Autonoma de Madrid, 28049 Madrid, Spain.
Zhuoning LiProteomics Innovation Laboratory and Proteomics Core, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Laura TufferyProteomics Innovation Laboratory and Proteomics Core, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Nan XuDevelopmental Biology Program & Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, New York, NY 10065, USA.
Elizabeth L CalderDevelopmental Biology Program & Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Johannes JungverdorbenDevelopmental Biology Program & Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Leslie WeberDevelopmental Biology Program & Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Aaron ZhongThe SKI Stem Cell Research Facility, The Center for Stem Cell Biology and Developmental Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
David G MiguezCentro de Biologia Molecular Severo Ochoa, Departamento de Fisica de la Materia Condensada, Instituto Nicolas Cabrera, and Condensed Matter Physics Center (IFIMAC), Universidad Autonoma de Madrid, 28049 Madrid, Spain.
Mara MonettiProteomics Innovation Laboratory and Proteomics Core, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ting ZhouDevelopmental Biology Program & Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; The SKI Stem Cell Research Facility, The Center for Stem Cell Biology and Developmental Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
Elisa GiacomelliDevelopmental Biology Program & Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Sean M. Healey and the AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: studerl@mskcc.org.
Lorenz StuderDevelopmental Biology Program & Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA. Electronic address: studerl@mskcc.org.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron (MN) loss. The most common genetic cause, a hexanucleotide repeat expansion in C9orf72 (C9-ALS), disrupts microglial function, contributing to neuroinflammation, a key disease driver. To investigate this, we developed a three-dimensional spinal microtissue (SM) model incorporating human induced pluripotent stem cell (hiPSC)-derived MNs, astrocytes, and microglia. Screening 190 Food and Drug Administration (FDA)-approved compounds, we identified sartans-angiotensin II receptor I blockers (ARBs)-as potent inhibitors of neuroinflammation. Telmisartan, a highly brain-penetrant ARB, significantly reduced the levels of pro-inflammatory cytokines interleukin (IL)-6 and IL-8 and rescued MN loss in C9-ALS SMs. Our findings suggest that C9-ALS microglia drive MN toxicity and that telmisartan can effectively mitigate inflammation and preserve MN viability. This work lays the groundwork for modeling disease-related neuroinflammation and points to telmisartan as a therapeutic candidate worth further exploration for treating C9-ALS.

Indexed as

Amyotrophic Lateral SclerosisC9orf72 ProteinInduced Pluripotent Stem CellsNeuroinflammatory DiseasesNeuroprotective AgentsSpinal CordTelmisartanAngiotensin II Type 1 Receptor BlockersAstrocytesHumansInflammationMicrogliaMotor NeuronsAngiotensin II Type 1 Receptor BlockersC9orf72 ProteinNeuroprotective AgentsTelmisartan3D microtissueamyotrophic lateral sclerosisastrocytesC9orf72drug screenmicrogliamotor neuronsneuroinflammationsartanstriculture

Identifiers

PMID40541176
PMCPMC12277806

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.