Evidence map›Paper›PMID 42277401›Full record

ArticleDiabetologia2026

Pharmacological inhibition of perforin dampens CD8

Prerak M Trivedi, Tara Catterall, Vivien R Sutton, Viki Moshovakis, Lorraine Elkerbout, Hedieh Akhlaghi, Julie A Spicer, Louis Boon, Thomas W H Kay, Joseph A Trapani and 1 more

Abstract read
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In one paragraph

Article in Diabetologia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Prerak M TrivediSt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia. ptrivedi@svi.edu.au.
Tara CatterallSt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
Vivien R SuttonCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Viki MoshovakisSt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
Lorraine ElkerboutSt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
Hedieh AkhlaghiCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Julie A SpicerAuckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Louis BoonJJP Biologics, Warsaw, Poland.
Thomas W H KaySt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
Joseph A TrapaniCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. joe.trapani@petermac.org.
Helen E ThomasSt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.

Funding

Breakthrough T1D 3-PDF-2024-1505-A-NNational Health and Medical Research Council 1175470National Health and Medical Research Council GNT1150425
6 · The paper itself

Abstract

aims/hypothesisCD8⁺ T cells are key mediators of beta cell destruction in type 1 diabetes, employing the perforin/granzyme and Fas/Fas ligand pathways. Evidence from our studies and others indicates that perforin plays a dominant role in CD8⁺ T cell mediated beta cell destruction in non-obese diabetic (NOD) mice. As perforin is indispensable for delivering pro-apoptotic granzymes into the cytosol of target cells, pharmacological inhibition of perforin may potentially protect beta cells against CD8

methodsThe new small molecule perforin inhibitor SN34960 was evaluated for its ability to protect the beta cells of non-obese diabetic mice upon attack by autoreactive cytotoxic T lymphocytes, both in vitro and in vivo.

resultsIn vitro, perforin inhibitor SN34960 protected isolated pancreatic islets from CD8 CONCLUSIONS/

interpretationOur results suggest that pharmacological perforin inhibition may represent a novel approach to protect beta cells from destruction by autoreactive CD8

Indexed as

CD8-Positive T-LymphocytesDiabetes Mellitus, Type 1Insulin-Secreting CellsPerforinAnimalsApoptosisFemaleMiceMice, Inbred NODT-Lymphocytes, CytotoxicPerforinApoptosisAutoimmunityBeta cellCytotoxic T lymphocyteFocused immunosuppressant drugGranzymeNOD mousePerforinType 1 diabetes

Identifiers

PMID42277401
PMCPMC13424576

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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.