Evidence map›Paper›PMID 35248547›Full record

Trial reportAmerican journal of ophthalmology2022

Three-Year Safety Results of SAR422459 (EIAV-ABCA4) Gene Therapy in Patients With ABCA4-Associated Stargardt Disease: An Open-Label Dose-Escalation Phase I/IIa Clinical Trial, Cohorts 1-5.

Maria A Parker, Laura R Erker, Isabelle Audo, Dongseok Choi, Saddek Mohand-Said, Kastytis Sestakauskas, Patrick Benoit, Terence Appelqvist, Melissa Krahmer, Caroline Ségaut-Prévost and 15 more

Open access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in American journal of ophthalmology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.4field-weighted citation impact, top 4% of its field
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

32 citing papers in PubMed, 54 citations in OpenAlex.

  1. Review
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  3. Article
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  9. Review
  10. Review
  11. Review
  12. "Seeing Stars": The Gene Therapy Revolution.Advances in experimental medicine and biology · 2025
    Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Stargardt macular dystrophy and therapeutic approaches.The British journal of ophthalmology · 2024
    Review
  19. Seeing the Future: A Review of Ocular Therapy.Bioengineering (Basel, Switzerland) · 2024
    Review
  20. Review
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

25 authors at 4 institutions in 2 countries.

Maria A ParkerFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.).
Laura R ErkerFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.).
Isabelle AudoINSERM, CNRS, Institut de la Vision, Sorborne Université, Paris, France (I.A., S.M.-S., P.O.-B., S.A.-S., J.A.S.).
Dongseok ChoiFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.); OHSU-PSU School of Public Health, Oregon Health & Science University, Portland, Oregon, USA (D.C.).
Saddek Mohand-SaidINSERM, CNRS, Institut de la Vision, Sorborne Université, Paris, France (I.A., S.M.-S., P.O.-B., S.A.-S., J.A.S.).
Kastytis SestakauskasSanofi R&D, TA MS, Neurology, Ophthalmology and Gene Therapy Development, France (K.S., P.B., C.S.-P.).
Patrick BenoitSanofi R&D, TA MS, Neurology, Ophthalmology and Gene Therapy Development, France (K.S., P.B., C.S.-P.).
Terence AppelqvistSanofi R&D, Translational Medicine and Early Development, Chilly-Mazarin (T.A.), France.
Melissa KrahmerFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.).
Caroline Ségaut-PrévostSanofi R&D, TA MS, Neurology, Ophthalmology and Gene Therapy Development, France (K.S., P.B., C.S.-P.).
Brandon J LujanFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.).
Ambar FaridiFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.); Veterans Affairs Portland Health Care System, Portland, Oregon (A.F.).
Elvira N ChegarnovFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.).
Peter N SteinkampFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.).
Cristy KuFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.).
Mariana Matioli da PalmaFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.).
Pierre-Olivier BaraleINSERM, CNRS, Institut de la Vision, Sorborne Université, Paris, France (I.A., S.M.-S., P.O.-B., S.A.-S., J.A.S.).
Sarah Ayelo-ScheerINSERM, CNRS, Institut de la Vision, Sorborne Université, Paris, France (I.A., S.M.-S., P.O.-B., S.A.-S., J.A.S.).
Andreas LauerFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.).
Tim StoutCullen Eye Institute, Baylor College of Medicine, Houston, Texas (T.S.), USA.
David J WilsonFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.).
Richard G WeleberFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.).
Mark E PennesiFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.).
José Alain SahelINSERM, CNRS, Institut de la Vision, Sorborne Université, Paris, France (I.A., S.M.-S., P.O.-B., S.A.-S., J.A.S.); Centre d'Investigation Clinique, Inserm-DGOS 1423, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, France (J.A.S.); Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA (J.A.S.). Electronic address: sahelja@upmc.edu.
Paul YangFrom the Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA (M.A.P., L.R.E., D.C., M.K., B.J.L., A.F., E.N.C., P.N.S., C.K., M.M.D., A.L., D.J.W., R.G.W., M.E.P., P.Y.). Electronic address: yangp@ohsu.edu.
Oregon Health & Science University · USCentre National de la Recherche Scientifique · FRSanofi (France) · FRBaylor College of Medicine · US

Funding

Proteomics CoreP30EY010572 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI John Peter Campbell · 1995 to 2026
$19.4M
Molecular mechanisms of retinal ON-bipolar cell signalingR01EY029985 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI DUVOISIN, ROBERT M, MORGANS, CATHERINE W · 2019 to 2023
$2.6M
Neuroprotective Mechanisms of Inosine Monophosphate Dehydrogenase Inhibitors in Retinitis PigmentosaK08EY026650 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI YANG, PAUL · 2016 to 2020
$1.1M
NEI NIH HHS K08 EY026650NEI NIH HHS P30 EY010572NEI NIH HHS R01 EY029985
6 · The paper itself

Abstract

purposeTo report on the safety of the first 5 cohorts of a gene therapy trial using recombinant equine infectious anemia virus expressing ABCA4 (EIAV-ABCA4) in adults with Stargardt dystrophy due to mutations in ABCA4.

designNonrandomized multicenter phase I/IIa clinical trial.

methodsPatients received a subretinal injection of EIAVABCA4 in the worse-seeing eye at 3 dose levels and were followed for 3 years after treatment.

main outcome measuresThe primary end point was ocular and systemic adverse events. The secondary end points were best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, multifocal ERG, color fundus photography, short-wavelength fundus autofluorescence, and spectral domain optical coherence tomography.

resultsThe subretinal injections were well tolerated by all 22 patients across 3 dose levels. There was 1 case of a treatment-related ophthalmic serious adverse event in the form of chronic ocular hypertension. The most common adverse events were associated with the surgical procedure. In 1 patient treated with the highest dose, there was a significant decline in the number of macular flecks as compared with the untreated eye. However, in 6 patients, hypoautofluorescent changes were worse in the treated eye than in the untreated eye. Of these, 1 patient had retinal pigment epithelium atrophy that was characteristic of tissue damage likely associated with bleb induction. No patients had any clinically significant changes in best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, or multifocal ERG attributable to the treatment.

conclusionsSubretinal treatment with EIAV-ABCA4 was well tolerated with only 1 case of ocular hypertension. No clinically significant changes in visual function tests were found to be attributable to the treatment. However, 27% of treated eyes showed exacerbation of retinal pigment epithelium atrophy on fundus autofluorescence. There was a significant reduction in macular flecks in 1 treated eye from the highest dose cohort. Additional follow-up and continued investigation in more patients will be required to fully characterize the safety and efficacy of EIAV-ABCA4.

Indexed as

Genetic TherapyStargardt DiseaseATP-Binding Cassette TransportersAtrophyElectroretinographyFluorescein AngiographyHumansInfectious Anemia Virus, EquineOcular HypertensionRetinal DegenerationTomography, Optical CoherenceVisual AcuityABCA4 protein, humanATP-Binding Cassette Transporters

Identifiers

PMID35248547
PMCPMC9308722
OpenAlexW4214952103

What OpenQuestion holds

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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.