September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Anatomical and functional effects of subretinal rAAV.sVEGFR-1 gene therapy on retinal-choroidal structures in nonhuman primates
Author Affiliations & Notes
  • Sharmila Vijay
    Avalanche Biotechnologies, Menlo Park, California, United States
  • Kathryn W Woodburn
    Avalanche Biotechnologies, Menlo Park, California, United States
  • Pallavi Sharma
    Avalanche Biotechnologies, Menlo Park, California, United States
  • Thomas Walter Chalberg
    Avalanche Biotechnologies, Menlo Park, California, United States
  • Vernard Woodley
    RxGen Inc, Hamden, Connecticut, United States
  • Jordan Attwood
    RxGen Inc, Hamden, Connecticut, United States
  • Matthew S Lawrence
    RxGen Inc, Hamden, Connecticut, United States
  • Mehdi Gasmi
    Avalanche Biotechnologies, Menlo Park, California, United States
  • Footnotes
    Commercial Relationships   Sharmila Vijay, Avalanche Biotechnologies (E); Kathryn Woodburn, Avalanche Biotechnologies (E); Pallavi Sharma, Avalanche Biotechnologies (E); Thomas Chalberg, Avalanche Biotechnologies (I), Avalanche Biotechnologies (C); Vernard Woodley, None; Jordan Attwood, None; Matthew Lawrence, None; Mehdi Gasmi, Avalanche Biotechnologies (E), Avalanche Biotechnologies (S)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3369. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Sharmila Vijay, Kathryn W Woodburn, Pallavi Sharma, Thomas Walter Chalberg, Vernard Woodley, Jordan Attwood, Matthew S Lawrence, Mehdi Gasmi; Anatomical and functional effects of subretinal rAAV.sVEGFR-1 gene therapy on retinal-choroidal structures in nonhuman primates. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3369.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Geographic atrophy has emerged as a potential complication in the chronic use of intravitreal VEGF inhibitors which are sometimes administered as frequently as every 4 weeks. This study was designed to determine whether this risk might exist in the setting of gene therapy vector-mediated expression of sVEGFR-1. The effect of sVEGFR-1 on the eye was evaluated for over a year following single dose subretinal administration of AVA-101 (rAAV.sVEGFR-1) adeno-associated virus (AAV) in nonhuman primates (NHPs).

Methods : One group received subretinal injections of vehicle (100 µL formulation buffer) in both eyes (n=3; 1F/2M) with a second group receiving subretinal injections of 1x1011 vg rAAV.sVEGFR-1 in the right eye (n=8; 4F/4M) and no injection in the left eye. Eyes were evaluated every three months by slit lamp exam, fundus imaging, optical coherence tomography (OCT) and full-field electroretinography (ERG). Vitreous sVEGFR-1 levels were evaluated at 12 months to confirm AAV transgene transduction with further assessments, including histopathology, at 18 months. Results up to 12 months are presented here.

Results : Subretinal administration of rAAV.sVEGFR-1 had no impact on the survival, clinical observations, clinical pathology, qualitative food consumption, retinal physiology as assessed by slit lamp exam, fundus imaging and OCT, or retinal function as assessed via ERG. Observed departures from normal findings were limited to injection-induced changes associated with physical introduction of the injection cannula into the retina, resulting in RPE disruption in the immediate track of the cannula in a few cases, and stippled alteration of the light reflex from the RPE within the bleb area. Two eyes, K484 OS (receiving vehicle) and K478 OD (receiving vector) exhibited injection-associated inflammatory changes which resolved by month 6.

Conclusions : Subretinal delivery of rAAV.sVEGFR-1 was well tolerated with no detectable geographic atrophy changes for over a year by a number of physiological and functional criteria. Histopathologic examination will occur at month 18 to further evaluate the chronic effects of continuous sVEGFR-1 expression.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×