Drug and Gene Delivery to the Back of the Eye: From Bench to Bedside

描述(申请人提供)：视网膜疾病，包括老年性黄斑变性，糖尿病视网膜病变，青光眼和遗传性视网膜世代是世界上导致失明的主要原因。随着预期寿命的延长和糖尿病流行的日益严重，视网膜疾病的社会经济负担预计将是巨大的。开发视网膜疾病治疗方法的限速步骤包括识别新的治疗剂以及将这些剂输送到眼后部组织的新方法。随着siRNA、miRNA和基因疗法等新的治疗剂的发现，对开发新的递送系统的需求也在升级。由于缺乏合适的递送系统，一些核酸疗法可能会失败，这些递送系统可以a)保护治疗剂免受核酸酶的降解，b)允许增强细胞进入，c)将非靶点效应降至最低，以及d)在治疗慢性视网膜疾病方面提供长期的递送。即使是像雷尼比珠单抗这样成功的蛋白质治疗剂，几年内频繁注射也可能对视网膜健康有害。通过开发蛋白质药物的长期给药方法，这一限制有可能被克服。对于小分子药物，眼后无创给药尚未成为临床现实。此外，即使是通过侵入性的方法，将小的水溶性分子持续输送到眼球后部也是一个重大挑战。为了加快新的小分子、蛋白质和核酸治疗药物从工作台到床边的转化，本次会议的目的是在包括来自学术界、产业界和监管机构的代表在内的不同参与者中分享基于药物产品开发原理的尖端科学。预计观众将来自不同的个人群体，包括那些代表少数群体和传统上在科学职业生涯中代表性较低的社区的人。为期两天的会议将包括口头和海报演示。为这次会议提供的资金支持将有助于招募顶尖科学家和与会者。此外，还将提供注册费减免和旅费奖励，以鼓励少数群体和代表性不足的社区参加。根据大会的发言和讨论情况，将在大会结束后3个月内编写白皮书，并及时提交眼科杂志发表。 公共卫生相关性：致盲视网膜疾病具有重大的社会经济影响。将新的治疗药物从试验台推向床边的一个限速步骤是将其输送到受影响的靶细胞。每一类治疗剂在开发临床可用的递送系统方面都提出了独特的问题。最近，基于siRNA的治疗取得了有限的成功，可能是因为它们对细胞表面的非靶点效应。这样的治疗剂应该进入细胞，同时避免与一些细胞表面受体相互作用。为了加速新的治疗药物的临床翻译，本次会议的目的是介绍基于科学的尖端方法来开发治疗眼背疾病的新药产品。

DESCRIPTION (provided by applicant): Retinal disorders including age related macular degeneration, diabetic retinopathy, glaucoma and inherited retinal generations are major causes of blindness in the world. With an increase in life expectancy and growing diabetes epidemic, the socioeconomic burden of retinal disorders is expected to enormous. Rate limiting steps in the development of treatments for retinal disorders include identification of new therapeutic agents as well as new approaches to deliver these agents to the tissues of the back of the eye. With the identification of new therapeutic agents such as siRNA, miRNA, and gene therapies, the need for the development of novel delivery systems also escalates. Several nucleic acid therapies may fail due to the lack of availability of appropriate delivery systems that can a) protect the therapeutic agent from degradation by nucleases, b) allow enhanced cellular entry, c) minimize off-target effects, and d) offer prolonged delivery in treating chronic retinal disorders. Even with successful protein therapeutic agents such as ranibizumab, frequent injections over several years might be detrimental to retinal health. This limitation can potentially be overcome through the development of long term delivery approaches for protein drugs. For small molecule drugs, noninvasive delivery to the back of the eye has yet to become a clinical reality. Further, sustaining the delivery of small water soluble molecules to the back of the eye even by invasive approaches is a major challenge. In order to expedite the translation of new small molecule, protein, and nucleic acid therapeutic agents from the bench to the bedside, the purpose of this conference is to share cutting edge science based on drug product development principles among a diverse group of participants, including representatives from academia, industry, and regulatory agencies. The audience is expected to be drawn from a diverse group of individuals including those representing minorities and traditionally underrepresented communities in science careers. The two day conference will include oral as well as poster presentations. Financial support provided for this conference will be helpful in recruiting top scientists as well as participants. In addition, registration fee waivers and travel awards will be provided in order to encourage participation by minorities and underrepresented communities. Based on the presentations and discussions at the conference, a white paper will be prepared within 3 months after the conference and submitted for publication in a timely manner in an ophthalmology journal. PUBLIC HEALTH RELEVANCE: Blinding retinal disorders have a major socioeconomic impact. A rate limiting step in advancing new therapeutic agents from bench to bedside is the delivery to the affected target cells. Each class of therapeutic agents poses unique problems in developing clinically usable delivery systems. Most recently, siRNA based therapies have met with limited success potentially due to their off-target effects on the cell surface. Such therapeutic agents should enter the cell, while avoiding interactions with some cell surface receptors. In order to expedite the clinical translation of new therapeutic agents, the purpose of this conference is to present cutting edge science based approaches for developing new drug products for treating back of the eye diseases.