Abstract
Presentation Description :
Inherited retinal dystrophies (IRDs) are associated with mutations in more than 280 genes causing progressive vision impairment and blindness. These genetically heterogeneous diseases destroy photoreceptors but leave intact and functional a significant number of inner retinal cells. In the past decade, converting by optogenetic technology the surviving inner retinal neurons into directly photosensitive cells has been demonstrated by many groups in ex-vivo and in-vivo models of IRDs. Our group at Institut de la Vision in Paris (José-Alain Sahel, Serge Picaud, Deniz Dalkara), together with Botond Roska at the Institute of Molecular and Clinical Ophthalmology Basel, developed a gene therapy approach for expressing photosensitive “optogenes” in one particular inner retinal cell type as a vision-restoration therapeutic approach. We genetically manipulated human retinal ganglion cells by delivering the “opto”protein ChrimsonR via adenovirus. This was combined with the use of light emitting goggles responding at all levels of lighting. Initial results of the clinical trial NCT03326336 evaluating the safety and tolerability of the combination product “GS030-Drug Product and GS030-Medical Device (engineered goggles)” showed that the optogenetic therapy partially restored vision to a 58-year-old man who had been diagnosed with Retinitis Pigmentosa 14 years earlier and whose vision was limited to rudimentary light perception. The study demonstrated that the patient regained the ability to recognize, count, locate and touch different objects with the treated eye and to detect where people stand, and that this was correlated with corresponding EEG signals. This was first evidence that optogenetic therapy can partially restore visual function in a patient with severe vision loss. Other patients demonstrating similar visual recovery are currently under evaluation. These first-in-human results for optogenetics pave the way for application in other diseases affecting excitable cells. Other groups are working on optogenetic or chemogenetic strategies. As a mutation-independent therapeutic strategy, optogenetics carries a great potential for treatment of a broad spectrum of retinal dystrophies with photoreceptor degeneration. It complements other gene-independent approaches e.g. neuroprotection by Rod-derived Cone Viability Factor potentially applicable at earlier stages.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.