Evidence map›Paper›PMID 40285355›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Truncated complement factor H Y402 gene therapy rescues C3 glomerulonephritis.

Lindsey A Chew, Daniel Grigsby, C Garren Hester, Joshua Amason, W Kyle McPherson, Edward J Flynn, Meike Visel, Christopher R Starr, John G Flannery, Tylor R Lewis and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Guarding glomeruli from immune injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Lindsey A ChewDepartment of Ophthalmology, Duke Eye Center, Duke University Medical Center, Durham, NC 27710, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Daniel GrigsbyGenetically Engineered Murine Model (GEMM) Core, University of Virginia, Charlottesville, VA 22903, USA.
C Garren HesterDepartment of Ophthalmology, Duke Eye Center, Duke University Medical Center, Durham, NC 27710, USA.
Joshua AmasonDepartment of Ophthalmology, Duke Eye Center, Duke University Medical Center, Durham, NC 27710, USA.
W Kyle McPhersonDepartment of Ophthalmology, Duke Eye Center, Duke University Medical Center, Durham, NC 27710, USA.
Edward J FlynnDepartment of Ophthalmology, Duke Eye Center, Duke University Medical Center, Durham, NC 27710, USA.
Meike ViselDepartment of Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Christopher R StarrDepartment of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
John G FlanneryDepartment of Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Tylor R LewisDepartment of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Catherine Bowes RickmanDepartment of Ophthalmology, Duke Eye Center, Duke University Medical Center, Durham, NC 27710, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: bowes007@duke.edu.

Funding

VISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI Goldis Malek · 1985 to 2026
$19.3M
Medical Scientist Training Program Training GrantT32GM145449 · NIGMS · DUKE UNIVERSITY · PI Christopher D Kontos · 2022 to 2026
$6.6M
Complement factor H modulates lipoprotein clearance in AMDR01EY031748 · NEI · DUKE UNIVERSITY · PI BOWES RICKMAN, CATHERINE · 2020 to 2024
$2.8M
Murine Age-related Macular Degeneration: Model of Known Human Risk FactorsR21EY017128 · NEI · DUKE UNIVERSITY · PI BOWES RICKMAN, CATHERINE · 2006 to 2007
$384k
NEI NIH HHS P30 EY005722NEI NIH HHS R01 EY031748NEI NIH HHS R21 EY017128NIGMS NIH HHS T32 GM145449
6 · The paper itself

Abstract

There are no effective therapies for patients with dry age-related macular degeneration (AMD) or C3 glomerulonephritis (C3G). Unfortunately, past efforts to treat C3G using exogenous human complement factor H (CFH) found limited success due to immune rejection of a foreign protein response. AMD research has also faced myriad challenges, including the absence of an ideal therapeutic target and difficulties with treatment delivery in certain preclinical models. In pursuit of an AMD therapy to overcome these obstacles, we ultimately capitalized on parallels in complement dysregulation between AMD and C3G. Here, we investigate the potential for CFH supplementation as a strategy to rescue C3G. Our findings demonstrate restored inhibition of complement's alternative pathway and long-term reversal of disease without immune rejection using adeno-associated virus (AAV)-mediated delivery of truncated CFH (tCFH) in a Cfh

Indexed as

Complement C3Complement Factor HGenetic TherapyGlomerulonephritisAnimalsComplement Pathway, AlternativeDependovirusDisease Models, AnimalGenetic VectorsHumansMacular DegenerationMiceMice, KnockoutCFH protein, humanComplement C3Complement Factor Hage-related macular degenerationC3 glomerulonephritisC3 glomerulopathycomplement factor Hcomplement regulationgene replacementgene therapy

Identifiers

PMID40285355
PMCPMC12461626

What Socratic 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 Socratic graph.