May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Clinical Trial of Gene Therapy for Early Onset Severe Retinal Dystrophy Caused by Defects in RPE65
Author Affiliations & Notes
  • J. W. Bainbridge
    UCL Institute of Ophthalmology and Moorfields Eye Hospital, London, United Kingdom
    NIHR Faculty, Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom
  • G. S. Rubin
    NIHR Faculty, Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom
    UCL Institute of Ophthalmology, London, United Kingdom
  • F. W. Fitzke
    NIHR Faculty, Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom
    UCL Institute of Ophthalmology, London, United Kingdom
  • G. E. Holder
    UCL Institute of Ophthalmology, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • A. Stockman
    UCL Institute of Ophthalmology, London, United Kingdom
  • S. S. Bhattacharya
    NIHR Faculty, Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom
    UCL Institute of Ophthalmology, London, United Kingdom
  • B. J. Carter
    Targeted Genetics Corporation, Seattle, Washington
  • A. T. Moore
    UCL Institute of Ophthalmology and Moorfields Eye Hospital, London, United Kingdom
    NIHR Faculty, Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom
  • R. R. Ali
    NIHR Faculty, Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom
    UCL Institute of Ophthalmology, London, United Kingdom
  • The Moorfields Eye Hospital / UCL Institute of Ophthalmology Study Group
    UCL Institute of Ophthalmology and Moorfields Eye Hospital, London, United Kingdom
  • Footnotes
    Commercial Relationships  J.W. Bainbridge, None; G.S. Rubin, None; F.W. Fitzke, None; G.E. Holder, None; A. Stockman, None; S.S. Bhattacharya, None; B.J. Carter, Targeted Genetics Corp., F; A.T. Moore, None; R.R. Ali, None.
  • Footnotes
    Support  UK Department of Health; The Wellcome Trust; Sir Jules Thorn Charitable Trust; British Retinitis Pigmentosa Soc; Fighting Blindness Ireland; Foundation Fighting Blindness; EU EVI-GenoRet and CliniGene
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1133. doi:https://doi.org/
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      J. W. Bainbridge, G. S. Rubin, F. W. Fitzke, G. E. Holder, A. Stockman, S. S. Bhattacharya, B. J. Carter, A. T. Moore, R. R. Ali, The Moorfields Eye Hospital / UCL Institute of Ophthalmology Study Group; Clinical Trial of Gene Therapy for Early Onset Severe Retinal Dystrophy Caused by Defects in RPE65. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1133. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : A number of previous studies have demonstrated that recombinant adeno-associated virus (rAAV) vector-mediated gene replacement therapy improves retinal function and visual behaviour in animal models of retinal degeneration caused by defects in the gene encoding RPE65. The purpose of this study is to determine whether gene therapy for retinal dystrophy caused by RPE65 mutations is safe and effective in humans.

Methods: : In a phase I/II dose-escalation trial, we have administered by subretinal injection a rAAV-2/2 vector expressing human RPE65 cDNA under the control of a human RPE65 promoter in 4 human subjects with early onset severe retinal dystrophy caused by mutations in RPE65. We have examined systemic vector dissemination and immune responses, assessed the effect of vector administration on visual function using a range of psychophysical techniques, and performed detailed electrophysiology and retinal imaging studies.

Results: : There have been no complications associated with the surgical delivery of vector in the subjects enrolled to date. We have detected no systemic dissemination of vector genome and no evidence of immune responses to rAAV vector capsid or RPE65 proteins. We have found no evidence of any significant adverse effect on retinal function.

Conclusions: : The outcomes in the first subjects to date suggest that subretinal administration of rAAV vector is safe in humans. We will report on further results of this ongoing trial as these become available.

Clinical Trial: : EudraCT 2006-001571-37

Keywords: retinal degenerations: hereditary • gene transfer/gene therapy • clinical (human) or epidemiologic studies: outcomes/complications 
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