Establishing channelrhodopsin as a tool to restore visual function

DESCRIPTION (provided by applicant): Eos Neuroscience, Inc., in collaboration with the company's academic partners, is developing a novel technology combining gene therapeutics and optical engineering techniques to restore the ability to see in people that are blind from photoreceptor diseases such as Retinitis Pigmentosa or Age-Related Macular Degeneration. It is the hope of our company that this technology will be widely applicable and available to the general public in the United States and worldwide that suffers from these debilitating and blinding diseases. In brief, Eos Neuroscience, Inc. is creating a technology that will restore photosensitivity in the remaining cells of the retina after the photoreceptors have died or are no longer functional, thus restoring the ability of the retina to respond to light stimulation. To this end, we are creating a delivery mechanism using an adeno-associated virus (AAV) that is proven safe and effective at delivering genes into cells. We will use this mechanism to get channelrhodopsin (ChR2), a light sensitive protein, into the spared, functioning cells of the retina. Additionally, we are working towards the required safety and efficacy data necessary to gain acceptance from the Food and Drug Administration (FDA) so that we can begin testing this technology in human subjects in the future. We have started this testing in mice and will continue to evaluate both physiological and behavioral measures. Accordingly, we propose the following specific aims for our SBIR Phase I project: 1) establish the AAV serotype(s) that lead to the best and most specific expression of our transgene in retinal bipolar cells, 2) measure efficacy of our gene therapy using both physiological and behavioral techniques, and 3) evaluate the basic safety of our gene therapy using histological and immunological measures. PUBLIC HEALTH RELEVANCE: Photoreceptor diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (ARMD) are becoming leading causes of blindness, affecting approximately 15 million people worldwide. Current therapies are targeting single genetic defects or are using electrical stimulation to restore visual function - neither of which is capable of being a treatment that can be applied broadly to photoreceptor disease. To this end, Eos Neuroscience, Inc. will establish a technology using channelrhodopsin, a light sensitive protein, to restore light sensitivity in patients suffering from photoreceptor degeneration, a technology that can be applied broadly and accurately for the treatment of these diseases.