Evidence map›Paper›PMID 41810513›Full record

ArticleClinical and experimental immunology2026

A novel fusion protein reduces kidney complement in experimental C3 glomerulopathy.

Talat H Malik, Karolina Kwiatkowska, Hannah J Lomax-Browne, Charlotte M Bottomley, Matthew Bright, Zhang Sung Tean, Ahmet K Akturk, Ian E Alexander, Grant J Logan, Matthew C Pickering

Abstract read
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In one paragraph

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

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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

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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

10 authors.

Talat H MalikCentre for Inflammatory Disease, Imperial College London, London, UK.
Karolina KwiatkowskaCentre for Inflammatory Disease, Imperial College London, London, UK.
Hannah J Lomax-BrowneCentre for Inflammatory Disease, Imperial College London, London, UK.
Charlotte M BottomleyCentre for Inflammatory Disease, Imperial College London, London, UK.
Matthew BrightCentre for Inflammatory Disease, Imperial College London, London, UK.
Zhang Sung TeanCentre for Inflammatory Disease, Imperial College London, London, UK.
Ahmet K AkturkCentre for Inflammatory Disease, Imperial College London, London, UK.
Ian E AlexanderGene Therapy Research Unit, Children's Medical Research Institute and Sydney Children's Hospitals Network, The University of Sydney, Westmead, NSW 2145, Australia.
Grant J LoganGene Therapy Research Unit, Children's Medical Research Institute and Sydney Children's Hospitals Network, The University of Sydney, Westmead, NSW 2145, Australia.
Matthew C PickeringCentre for Inflammatory Disease, Imperial College London, London, UK.ORCID 0000-0002-1153-0192

Funding

Rebecca L. Cooper Foundation PG2019449Wellcome TrustWellcome Trust Senior Fellowship in Clinical Science 212252/Z/18/Z
6 · The paper itself

Abstract

Complement activation contributes to kidney damage in many types of glomerulonephritis and complement inhibition therapy is approved for IgA nephropathy and C3 glomerulopathy. However, inhibition is not specific to the kidney resulting in unnecessary systemic complement inhibition and increased infection risk. To develop an effective inhibitor of glomerular complement we combined complement factor H-related protein 5 (FHR51-9), which binds to glomerular complement C3, with the complement regulatory domains of the key negative regulator of C3 activation complement factor H (FH1-5). One week after adeno-associated virus (AAV) mediated expression of the FHR51-9FH1-5 fusion protein in factor H (FH)-deficient mice, glomerular C3b/iC3b/C3c was significantly reduced and properdin resolved completely compared to controls. There was no change to circulating C3 levels and FHR51-9FH1-5 was detected in glomeruli in association with C3d. Six and twenty weeks after AAV8-FHR51-9FH1-5 treatment in hFH-FHR5mut mice (a mouse model of CFHR5 nephropathy) glomerular C3b/iC3b/C3c, C3d, and C5 were significantly reduced and properdin resolved completely compared to controls. Pre-administration of AAV-FHR51-9FH1-5 also ameliorated abnormal glomerular C3b/iC3b/C3c, C3d, C5, and properdin in a triggered CFHR5 nephropathy model. In vitro FHR51-9FH1-5 showed dose-dependent binding to surface-immobilized C3, C3b, iC3b, and C3d; factor I cofactor activity; and reduced C3a generation in an alternative pathway convertase assay. Taken together, the FHR51-9FH1-5 protein reduced glomerular C3 in experimental models of C3 glomerulopathy driven by either FH deficiency or mutated FHR5. These preclinical data indicate that FHR51-9FH1-5 protein represents a novel treatment strategy for complement-mediated kidney disease.

Indexed as

Complement C3Complement Factor HGlomerulonephritisKidney GlomerulusRecombinant Fusion ProteinsAnimalsComplement ActivationDependovirusDisease Models, AnimalHumansKidneyMiceMice, Inbred C57BLMice, KnockoutProperdinComplement C3Complement Factor HProperdinRecombinant Fusion Proteinscomplementglomerulonephritistherapy

Identifiers

PMID41810513
PMCPMC13020681

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Registered trials

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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.