Establishing channelrhodopsin as a tool to restore visual function

描述(申请人提供)：Eos NeuroScience，Inc.与该公司的学术合作伙伴合作，正在开发一种结合基因疗法和光学工程技术的新技术，以恢复因视网膜色素变性或老年性黄斑变性等感光疾病而失明的人的视力。我们公司希望，这项技术将广泛适用于美国和世界各地患有这些衰弱和致盲疾病的普通公众。简而言之，Eos NeuroScience，Inc.正在创造一种技术，在感光器死亡或不再起作用后，将恢复视网膜剩余细胞的光敏性，从而恢复视网膜对光刺激的反应能力。为此，我们正在创造一种使用腺相关病毒(AAV)的传递机制，这种病毒被证明在将基因传递到细胞方面是安全和有效的。我们将使用这一机制将视紫红质(ChR2)--一种光敏蛋白--带入视网膜的备用、正常运作的细胞。此外，我们正在努力获得必要的安全性和有效性数据，以获得食品和药物管理局(FDA)的认可，以便我们可以在未来开始在人体受试者中测试这项技术。我们已经开始在老鼠身上进行这项测试，并将继续评估生理和行为指标。因此，我们为SBIR第一阶段项目提出了以下具体目标：1)建立导致我们的转基因在视网膜双极细胞中最佳和最特异表达的AAV血清型(S)，2)使用生理和行为技术衡量我们基因治疗的有效性，以及3)使用组织学和免疫学方法评估我们基因治疗的基本安全性。公共卫生相关性：视网膜色素变性(RP)和老年性黄斑变性(ARMD)等感光性疾病正成为导致失明的主要原因，全球约有1500万人受到影响。目前的治疗方法是针对单一的基因缺陷或使用电刺激来恢复视觉功能--这两种方法都不能广泛应用于光感受器疾病的治疗。为此，Eos神经科学公司将建立一种技术，使用一种光敏蛋白质--通道视紫红质，恢复光感受器变性患者的光敏感性，这项技术可以广泛而准确地应用于这些疾病的治疗。

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.