PIPELINE

Gene Therapy for Retinitis Pigmentosa

Our gene therapy approach to Retinitis Pigmentosa (RP): Optogenetics

Our gene therapy program is an optogenetic approach for the treatment of RP. Optogenetics is the practice of inducing light sensitivity in cells that were previously not sensitive to light. Optogenetics is used extensively outside of ophthalmology for various research initiatives involving cellular electrical signaling. It has recently been applied to ophthalmology as a potential therapy for inherited retinal degenerative diseases.

An optimized adeno-associated virus will be used to deliver human rhodopsin (hRho) to the ON bipolar cells of the retina(1). The bipolar neurons are immediately downstream of photoreceptors in visual signaling. Since the photoreceptors are dying or dead in RP patients, this technology would make the next neuron in the signaling cascade light sensitive. Expression of hRho in the ON bipolar cells is expected to restore some level of light sensitivity to the patient(2). The signal amplification may also benefit signal quality, particularly at lower light levels than other optogenetic approaches. Similar to other optogenetic technologies but unlike many other gene therapies, our approach is independent of genotype. Since hRho is an endogenous human protein native to the retina, hRho could lower the immunological risk of such a therapy, enabling us to develop a potentially safe and effective treatment for vision restoration in advanced RP patients.

(1) Vandenberghe LH, Auricchio A. Novel adeno-associated viral vectors for retinal gene therapy. Gene Ther. 2012 Feb;19(2):162-8

(2) Cehajic-Kapetanovic J, Eleftheriou C, Allen AE, Milosavljevic N, Pienaar A, Bedford R, Davis KE, Bishop PN, Lucas RJ. Restoration of Vision with Ectopic Expression of Human Rod Opsin. Curr Biol. 2015 Aug 17;25(16):2111-22