Abstract
Purpose :
To evaluate the effect of EXG102-031 on exudative retinal detachment in Tet/opsin/VEGF double transgenic mice with doxycycline-induced expression of high levels of VEGF-A
Methods :
EXG102-031 is an AAV-based gene therapeutic vector expressing a fusion protein that is able to bind all subtypes of VEGF as well as the angiopoietin 2. Adult Tet/opsin/VEGF mice (n = 8-12/group) were given a subretinal injection of EXG102-031 of 1 × 108, 3 × 108, 1 × 109, 3 × 109, 6 ×109 and 7 ×109 vg/eye, or 5×109 vg/eye of the positive control vector, AV8-anti-VEGFfab, in one eye, and the negative control vector AAV2-Luc in the other eye. Four weeks post injection, the mice were given doxycycline to turn on expression of VEGF in photoreceptors. Four days later, mice were anesthetized, pupils dilated, and fundus photographs were obtained with a Micron III Retinal Imaging Microscope (Phoenix Research Laboratories, Pleasanton, CA). Images were graded by a masked investigator for the presence of total, partial, or no exudative retinal detachment.
Results :
EXG102-031 for all dosages ranging from 1×108 to 7 ×109 vg/eye resulted in dose-related suppression of retinal detachment. Total retinal detachment was reduced by 80% after injection of 1×109 and 100% after injection of 7 ×109 vg of EXG102-031. Mice in the positive control group received AV8-antiVEGFfab vector at a dose of 5×109 vg/eye showed an inhibitory effect on retinal detachment comparable to that found in the 1×109 and 3×109 dose groups received EXG102-031. These data strongly support clinical development of gene therapy with EXG102-031 for treatment of patients with neovascular AMD.
Conclusions :
These data strongly support clinical development of gene therapy with EXG102-031 for treatment of patients with neovascular AMD.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.