Evidence map›Paper›PMID 40914166›Full record

ArticleCell reports. Medicine2025

Development of a cyst-targeted therapy for polycystic kidney disease using an antagonistic dimeric IgA monoclonal antibody against cMET.

Margaret F Schimmel, Bryan C Bourgeois, Alison K Spindt, Sage A Patel, Tiffany Chin, Gavin E Cornick, Yuqi Liu, Thomas Weimbs

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Margaret F SchimmelDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Bryan C BourgeoisDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Alison K SpindtDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Sage A PatelDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Tiffany ChinDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Gavin E CornickDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Yuqi LiuDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Thomas WeimbsDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA. Electronic address: weimbs@ucsb.edu.

Funding

Ketosis as a therapy for polycystic kidney diseaseR01DK124895 · NIDDK · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI WEIMBS, THOMAS · 2020 to 2024
$2.2M
NIDDK NIH HHS R01 DK124895
6 · The paper itself

Abstract

Polycystic kidney disease (PKD) is characterized by the development of fluid-filled kidney cysts and relentless progression to renal failure. Current treatments have adverse effects and limited efficacy, enhancing the need for improved therapeutics. Here, we provide a proof of concept for the use of dimeric immunoglobulin A (IgA) (dIgA) monoclonal antibodies (mAbs) to target epithelial-enclosed cysts, by exploiting their ability to transcytose via the polymeric immunoglobulin receptor highly expressed on renal cyst-lining cells. We engineered an antagonistic dIgA mAb against the cell mesenchymal-epithelial transition (cMET) receptor, a driver of cyst progression, and demonstrated its specific binding and inhibition of cMET in vitro. In vivo studies in PKD rodent models showed efficient targeting of the mAb to renal cyst lumens and its ability to slow disease progression without apparent adverse effects. This study presents an intriguing avenue for developing antibody-based therapies for PKD and similar diseases by repurposing existing immunoglobulin G (IgG) mAbs into dIgA mAbs for superior targeting to epithelial-enclosed compartments.

Indexed as

Antibodies, MonoclonalCystsImmunoglobulin APolycystic Kidney DiseasesAnimalsDisease Models, AnimalEpithelial-Mesenchymal TransitionHumansMaleMiceRatsAntibodies, MonoclonalImmunoglobulin AcMETcyst targetingdimeric IgAdrug deliverymonoclonal antibody therapymucosal immunotherapypIgRPKD

Identifiers

PMID40914166
PMCPMC12490227

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.