Abstract
Purpose :
The PIONEER study evaluates the safety and tolerability of GS030, an investigational optogenetic treatment combining a gene therapy and a light-stimulation medical device in subjects with late-stage non-syndromic retinitis pigmentosa (RP).
Methods :
PIONEER is a Phase 1/2a open-label study including three dose-escalation cohorts (5E10, 1.5E11, 5E11 vg/eye) of 3 subjects each, and an extension cohort treated at the highest tolerated dose. Treatment is gene agnostic, and the optogenetic gene therapy encoding channelrhodopsin ChrimsonR-tdTomato (ChRtdT) is administered by intravitreal injection to target preserved retinal ganglion cells (RGCs). While RGCs are normally not light sensitive cells, expression of ChRtdT renders RGCs sensitive to light. After GS030 optogentic therapy, controlled stimulation of the genetically reengineered retina using a visual interface stimulating goggles encode images of the visual world in real time and project them onto the retina by modulating a tailored light source at a specific wavelength, and mimicking natural visual processing.
Results :
As of July 2020, six patients in the first two cohorts and one patient of the third cohort were treated with a single intravitreal injection of optogentic gene therapy in their worse-seeing eye. Use of the visual interface medical device to stimulate RGCs expressing ChR-tdT was initiated two months after gene therapy injection and showed no safety concerns, before or after injection. Up to 2 years after gene therapy administration, no adverse event led to study discontinuation. The most common adverse events were mild or moderate anterior chamber or vitreous inflammation (4/7 patients) responsive to corticosteroid treatment, and transitory mild sensitivity to light (2/7 patients) that started before the use of light stimulation by the visual interface goggles.
Conclusions :
The PIONEER study is the first clinical trial combining a gene therapy and a medical device using an optogenetic approach. The treatment was well tolerated up to two years after gene therapy administration.
This is a 2021 ARVO Annual Meeting abstract.