Evidence map›Paper›PMID 24439297›Full record

Trial reportLancet (London, England)2014

Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial.

Robert E MacLaren, Markus Groppe, Alun R Barnard, Charles L Cottriall, Tanya Tolmachova, Len Seymour, K Reed Clark, Matthew J During, Frans P M Cremers, Graeme C M Black and 4 more

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Lancet (London, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 423 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
423citing papers in PubMed, 8 pooled it
45.1field-weighted citation impact, top 1% 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.

NCT01461213 phase1 / phase2completednot on this map

An Open Label Dose Escalation Phase 1 Clinical Trial of Retinal Gene Therapy for Choroideraemia Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein 1 (REP1)

TypeinterventionalSponsorUniversity of OxfordRan2011 to 2017Enrolled14ConditionsChoroideremiaArmsrAAV2.REP1
NCT02077361 phase1 / phase2completednot on this mapstarted 2015, after this paper: background citation

An Open Label Clinical Trial of Retinal Gene Therapy for Choroideremia Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein-1 (REP1)

TypeinterventionalSponsorUniversity of AlbertaRan2015 to 2022Enrolled6ConditionsChoroideremiaArmsrAAV2.REP1 vector
3 · Its place in the literature

Who cites it

423 citing papers in PubMed, 8 syntheses or guidelines pooled it, 771 citations in OpenAlex.

  1. A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
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  14. Vitrectomy and internal limiting membrane peeling for extensive macular schisis in choroideremia.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
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  15. Review
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  19. Gene therapy in patients with choroideremia: a meta-analysis of clinical trials.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
    Article
  20. Review

363 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 10 institutions in 4 countries.

Robert E MacLarenNuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Oxford Eye Hospital, Oxford University Hospitals NHS Trust and NIHR Biomedical Research Centre, Oxford, UK; Moorfields Eye Hospital NHS Foundation Trust and NIHR Ophthalmology Biomedical Research Centre, London, UK. Electronic address: enquiries@eye.ox.ac.uk.
Markus GroppeNuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Oxford Eye Hospital, Oxford University Hospitals NHS Trust and NIHR Biomedical Research Centre, Oxford, UK; Moorfields Eye Hospital NHS Foundation Trust and NIHR Ophthalmology Biomedical Research Centre, London, UK.
Alun R BarnardNuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Charles L CottriallOxford Eye Hospital, Oxford University Hospitals NHS Trust and NIHR Biomedical Research Centre, Oxford, UK.
Tanya TolmachovaMolecular Medicine Section, National Heart and Lung Institute, Imperial College London, London, UK.
Len SeymourDepartment of Oncology, University of Oxford, Oxford, UK.
K Reed ClarkResearch Institute at the Nationwide Children's Hospital, Columbus, OH, USA.
Matthew J DuringCollege of Medicine, Ohio State University Medical Center, Columbus, OH, USA.
Frans P M CremersDepartment of Human Genetics and Nijmegen Center for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.
Graeme C M BlackManchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester, UK.
Andrew J LoteryClinical Neurosciences Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Susan M DownesNuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Oxford Eye Hospital, Oxford University Hospitals NHS Trust and NIHR Biomedical Research Centre, Oxford, UK.
Andrew R WebsterMoorfields Eye Hospital NHS Foundation Trust and NIHR Ophthalmology Biomedical Research Centre, London, UK; UCL Institute of Ophthalmology, London, UK.
Miguel C SeabraMolecular Medicine Section, National Heart and Lung Institute, Imperial College London, London, UK; Chronic Diseases Research Centre, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.
University of Oxford · GBMoorfields Eye Hospital NHS Foundation Trust · GBOxford University Hospitals NHS Trust · GBImperial College London · GBNationwide Children's Hospital · USRadboud University Medical Center · NLSt Mary's Hospital · GBThe Ohio State University Wexner Medical Center · USUniversidade Nova de Lisboa · PTUniversity of Southampton · GB

Funding

Cancer Research UK 11339Department of HealthWellcome Trust 091984
6 · The paper itself

Abstract

backgroundChoroideremia is an X-linked recessive disease that leads to blindness due to mutations in the CHM gene, which encodes the Rab escort protein 1 (REP1). We assessed the effects of retinal gene therapy with an adeno-associated viral (AAV) vector encoding REP1 (AAV.REP1) in patients with this disease.

methodsIn a multicentre clinical trial, six male patients (aged 35-63 years) with choroideremia were administered AAV.REP1 (0·6-1·0×10(10) genome particles, subfoveal injection). Visual function tests included best corrected visual acuity, microperimetry, and retinal sensitivity tests for comparison of baseline values with 6 months after surgery. This study is registered with ClinicalTrials.gov, number NCT01461213.

findingsDespite undergoing retinal detachment, which normally reduces vision, two patients with advanced choroideremia who had low baseline best corrected visual acuity gained 21 letters and 11 letters (more than two and four lines of vision). Four other patients with near normal best corrected visual acuity at baseline recovered to within one to three letters. Mean gain in visual acuity overall was 3·8 letters (SE 4·1). Maximal sensitivity measured with dark-adapted microperimetry increased in the treated eyes from 23·0 dB (SE 1·1) at baseline to 25·3 dB (1·3) after treatment (increase 2·3 dB [95% CI 0·8-3·8]). In all patients, over the 6 months, the increase in retinal sensitivity in the treated eyes (mean 1·7 [SE 1·0]) was correlated with the vector dose administered per mm(2) of surviving retina (r=0·82, p=0·04). By contrast, small non-significant reductions (p>0·05) were noted in the control eyes in both maximal sensitivity (-0·8 dB [1·5]) and mean sensitivity (-1·6 dB [0·9]). One patient in whom the vector was not administered to the fovea re-established variable eccentric fixation that included the ectopic island of surviving retinal pigment epithelium that had been exposed to vector.

interpretationThe initial results of this retinal gene therapy trial are consistent with improved rod and cone function that overcome any negative effects of retinal detachment. These findings lend support to further assessment of gene therapy in the treatment of choroideremia and other diseases, such as age-related macular degeneration, for which intervention should ideally be applied before the onset of retinal thinning.

fundingUK Department of Health and Wellcome Trust.

Indexed as

Adaptor Proteins, Signal TransducingAdenoviridaeAdultAgedChoroideremiaFluorescenceGenetic TherapyGenetic VectorsGene Transfer TechniquesHumansInjections, IntraocularMaleMiddle AgedRetinal DetachmentTransgenesVisual AcuityAdaptor Proteins, Signal TransducingCHM protein, human

Identifiers

PMID24439297
PMCPMC4171740
OpenAlexW2126115955

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.