June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Evaluation of electroretinography in cynomolgus monkeys after subretinal injection of rAAV.hPDE6A
Author Affiliations & Notes
  • Tobias Peters
    Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany
    STZ eyetrial at the Centre for Ophthalmology, , University of Tübingen, Germany, Tuebingen, Germany
  • Barbara Wilhelm
    STZ eyetrial at the Centre for Ophthalmology, , University of Tübingen, Germany, Tuebingen, Germany
  • birgit niggemann
    Covance Preclinical Services GmbH, Muenster, Germany
  • Sven Korte
    Covance Preclinical Services GmbH, Muenster, Germany
  • Karl Ulrich Bartz-Schmidt
    University Eye Hospital, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany
  • Stylianos Michalakis
    Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany
  • Guy Alex Ochakovski
    University Eye Hospital, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany
  • Dominik M Fischer
    University Eye Hospital, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany
    Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany
  • Footnotes
    Commercial Relationships   Tobias Peters, None; Barbara Wilhelm, None; birgit niggemann, None; Sven Korte, None; Karl Bartz-Schmidt, None; Stylianos Michalakis, Eyeserv GmbH (P); Guy Alex Ochakovski, None; Dominik Fischer, None
  • Footnotes
    Support  Tistou and Charlotte Kerstan Foundation
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4096. doi:
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    • Get Citation

      Tobias Peters, Barbara Wilhelm, birgit niggemann, Sven Korte, Karl Ulrich Bartz-Schmidt, Stylianos Michalakis, Guy Alex Ochakovski, Dominik M Fischer; Evaluation of electroretinography in cynomolgus monkeys after subretinal injection of rAAV.hPDE6A. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4096.

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

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Abstract

Purpose : A GLP conform toxicological study was performed in non-human primates (NHP) after subretinal injection of rAAV.hPDE6A in order to explore safety issues for implementation of a phase I/II clinical gene therapy trial.

Methods : 22 purpose-bread NHPs (macaca fascicularis) were allocated to either control (n=3 per sex) receiving vehicle only, low dose (1x1011 total vector genomes (vg)) or high dose (1x1012 vg) groups (n=4 per sex). Each test item cohort (subretinal dosing on day 1 only) consisted of 4 animals per sex. GLP-compliant, scotopic and photopic fullfield electroretinographic recordings (ERGs) were obtained during the pre-dose phase, and at 4 and 12 weeks after dosing. Rod function were recorded in response to increasing light intensities in dark adapted state as well as cone responses after light adaptation, according to the recommendations of the ERG- Standard of the International Society for Clinical Electrophysiology of Vision (ISCEV).

Results : In one animal of the control group retinal atrophy in the treated eye resulted in about 60% reduced ERG amplitudes. ERG results of all treated animals showed no signs of severe deterioration. No significant changes could be seen in implicit times in any response, indicating a well-preserved function of the responding cell population in each animal.

Conclusions : Fullfield ERG as a summed potential is able to detect relevant and irreversible deterioration of retinal function. No signs of irreversible damage could be seen up to 12 weeks after subretinal injection of rAAV.hPDE6A. This supports the notion that PDE6A gene therapy with the vector used is safe in non-human primates.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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