April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Visually-Guided Mobility in Patients Treated With Gene Therapy for Leber's Congenital Amaurosis
Author Affiliations & Notes
  • G. S. Rubin
    Visual Neuroscience,
    UCL Institute of Ophthalmology, London, United Kingdom
  • J. W. Bainbridge
    Div of Molecular Therapy,
    UCL Institute of Ophthalmology, London, United Kingdom
  • H. Roche
    Visual Neuroscience,
    UCL Institute of Ophthalmology, London, United Kingdom
  • S. J. Robbie
    Div of Molecular Therapy,
    UCL Institute of Ophthalmology, London, United Kingdom
  • A. T. Moore
    Ophthalmology,
    UCL Institute of Ophthalmology, London, United Kingdom
  • T. Fujiyama
    Department of Civil and Environmental Engineering, University College London, London, United Kingdom
  • N. Tyler
    Department of Civil and Environmental Engineering, University College London, London, United Kingdom
  • R. R. Ali
    Div of Molecular Therapy,
    UCL Institute of Ophthalmology, London, United Kingdom
  • Footnotes
    Commercial Relationships  G.S. Rubin, None; J.W. Bainbridge, U.S. patent application assigned to University College London and Targeted Genomics Corporation entitled, "Devices and methods for delivering polynucleotides into retinal cells of the macula and fovea, P; H. Roche, None; S.J. Robbie, None; A.T. Moore, None; T. Fujiyama, None; N. Tyler, None; R.R. Ali, U.S. patent application assigned to University College London and Targeted Genomics Corporation entitled, "Devices and methods for delivering polynucleotides into retinal cells of the macula and fovea, P.
  • Footnotes
    Support  NIHR Biomedical Research Centre for Ophthalmology, London and Engineering and Physical Sciences Research Council, UK
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 1392. doi:
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      G. S. Rubin, J. W. Bainbridge, H. Roche, S. J. Robbie, A. T. Moore, T. Fujiyama, N. Tyler, R. R. Ali; Visually-Guided Mobility in Patients Treated With Gene Therapy for Leber's Congenital Amaurosis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1392.

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Abstract

Purpose: : We and others have previously shown that gene therapy can improve retinal sensitivity in human patients with inherited retinal dystrophy caused by a defect in the gene encoding RPE65. Here we describe a test for visually-guided mobility used to assess the functional capabilities of patients treated with gene therapy.

Methods: : Patients with inherited retinal dystrophy are participating in a phase I/II dose escalation trial of a subretinally delivered rAAV vector expressing RPE65. Prior to treatment and at 6, 12, and 24 months after treatment, the patients undergo a mobility evaluation at the Pedestrian Accessibility and Movement Environment Laboratory (PAMELA) at University College London. PAMELA consists of a 80 sq m raised platform with concrete paving stones and street lamps to simulate an outdoor sidewalk environment at controlled levels of illumination. For our study, the platform was configured as three mobility tasks selected as a result of a study of pedestrian movement tasks - a straight walk through an open doorway, a serpentine course through a simple maze, and a straight walk along a path with simulated curbstones. Illumination levels ranging from 240 lux to 2 lux were tested. The time to complete each section and the number of navigation errors were recorded. Testing was performed monocularly in counterbalanced order.

Results: : Prior to treatment, mobility performance is within normal limits for 5 of 7 patients patients at 240 lux but travel time and mobility errors increase rapidly with decreasing illumination such that none of the patients navigate successfully at 4 lux (standard residential street lighting). Following treatment 3 of 7 patients show significant improvement with all three successfully navigating at 4 lux and 1 patient able to traverse the course without error at 2 lux, albeit 51% slower than normally-sighted controls. All of the patients who showed an improvement in mobility also had improved retinal sensitivity measured by microperimetry.

Conclusions: : The results suggest that gene therapy increases retinal sensitivity in some patients and this leads to improved visually-guided mobility under nighttime lighting conditions.

Clinical Trial: : www.clinicaltrials.gov NCT00643747

Keywords: gene transfer/gene therapy • low vision • retinal degenerations: hereditary 
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