Evidence map›Paper›PMID 30196853›Full record

Trial reportMolecular therapy : the journal of the American Society of Gene Therapy2018

Retinal AAV8-RS1 Gene Therapy for X-Linked Retinoschisis: Initial Findings from a Phase I/IIa Trial by Intravitreal Delivery.

Catherine Cukras, Henry E Wiley, Brett G Jeffrey, H Nida Sen, Amy Turriff, Yong Zeng, Camasamudram Vijayasarathy, Dario Marangoni, Lucia Ziccardi, Sten Kjellstrom and 8 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02317887 (A Phase I/IIa Study of RS1 Ocular Gene Transfer for X-linked Retinoschisis), which is not on this map. Cited by 165 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
165citing papers in PubMed, 4 pooled it
10.3field-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.

NCT02317887 phase1 / phase2completednot on this map

A Phase I/IIa Study of RS1 Ocular Gene Transfer for X-linked Retinoschisis

TypeinterventionalSponsorVegaVect, Inc.Ran2015 to 2024Enrolled12ConditionsRetinoschisis, X-LinkedArmsRS1 AAV Vector
3 · Its place in the literature

Who cites it

165 citing papers in PubMed, 4 syntheses or guidelines pooled it, 261 citations in OpenAlex.

  1. Pooled it
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  5. Immune function in X-linked retinoschisis subjects in an AAV8-RS1 phase I/IIa gene therapy trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
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105 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 4 countries.

Catherine CukrasNIH, National Eye Institute, Bethesda, MD 20892, USA.
Henry E WileyNIH, National Eye Institute, Bethesda, MD 20892, USA.
Brett G JeffreyNIH, National Eye Institute, Bethesda, MD 20892, USA.
H Nida SenNIH, National Eye Institute, Bethesda, MD 20892, USA.
Amy TurriffNIH, National Eye Institute, Bethesda, MD 20892, USA.
Yong ZengSTRRMD/NIDCD/NIH, Bethesda, MD 20874, USA.
Camasamudram VijayasarathySTRRMD/NIDCD/NIH, Bethesda, MD 20874, USA.
Dario MarangoniSTRRMD/NIDCD/NIH, Bethesda, MD 20874, USA.
Lucia ZiccardiNeurophysiology of Vision and Neuropathmology Unit, IRCCS Fondazione G.B. Bietti, Rome 00198, Italy.
Sten KjellstromDepartment of Ophthalmology, Lund University, Lund, Sweden.
Tae Kwon ParkOphthalomology, Soonchunhyang University Bucheon Hospital, Seoul, Korea.
Suja HiriyannaOcular Gene Therapy Core, National Eye Institute, Bethesda, MD 20892, USA.
J Fraser WrightOphthalomology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Peter ColosiOcular Gene Therapy Core, National Eye Institute, Bethesda, MD 20892, USA.
Zhijian WuNIH, National Eye Institute, Bethesda, MD 20892, USA.
Ronald A BushSTRRMD/NIDCD/NIH, Bethesda, MD 20874, USA.
Lisa L WeiNIH, National Eye Institute, Bethesda, MD 20892, USA.
Paul A SievingNIH, National Eye Institute, Bethesda, MD 20892, USA. Electronic address: paulsieving@nei.nih.gov.
National Eye Institute · USNational Institute on Deafness and Other Communication Disorders · USChildren's Hospital of Philadelphia · USFondazione G.B. Bietti · ITLund University · SESoonchunhyang University Hospital · KR

Funding

Retinal Gene TherapyZIAEY000443 · NEI · NATIONAL EYE INSTITUTE · PI LI, TIANSEN · 2009 to 2020
$8.4M
Pathophysiology and Treatment of Retinal Degenerations in Animal ModelsZIADC000077 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI SIEVING, PAUL · 2009 to 2019
$3.2M
Retinal Degeneration--genetic/environmental animal modelZ01DC000065 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI SIEVING, PAUL · 2002 to 2008
$2.5M
Intramural NIH HHS Z01 DC000065
6 · The paper itself

Abstract

This study evaluated the safety and tolerability of ocular RS1 adeno-associated virus (AAV8-RS1) gene augmentation therapy to the retina of participants with X-linked retinoschisis (XLRS). XLRS is a monogenic trait affecting only males, caused by mutations in the RS1 gene. Retinoschisin protein is secreted principally in the outer retina, and its absence results in retinal cavities, synaptic dysfunction, reduced visual acuity, and susceptibility to retinal detachment. This phase I/IIa single-center, prospective, open-label, three-dose-escalation clinical trial administered vector to nine participants with pathogenic RS1 mutations. The eye of each participant with worse acuity (≤63 letters; Snellen 20/63) received the AAV8-RS1 gene vector by intravitreal injection. Three participants were assigned to each of three dosage groups: 1e9 vector genomes (vg)/eye, 1e10 vg/eye, and 1e11 vg/eye. The investigational product was generally well tolerated in all but one individual. Ocular events included dose-related inflammation that resolved with topical and oral corticosteroids. Systemic antibodies against AAV8 increased in a dose-related fashion, but no antibodies against RS1 were observed. Retinal cavities closed transiently in one participant. Additional doses and immunosuppressive regimens are being explored to pursue evidence of safety and efficacy (ClinicalTrials.gov: NCT02317887).

Indexed as

AdultAgedEye ProteinsFemaleGenetic TherapyHumansIntravitreal InjectionsMaleMiddle AgedMutationRetinaRetinoschisisYoung AdultEye ProteinsRS1 protein, humanAAV vectorclinical trialgene therapyocular diseaseretinal diseaseX-linked retinoschisis

Identifiers

PMID30196853
PMCPMC6127971
OpenAlexW2840212422

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.