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

药物和基因输送到眼后部：从实验室到床边

• 批准号: 8203523
• 负责人: UDAY B KOMPELLA
• 金额: $ 3.39万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8203523
• 关键词: Academia; Address; Affect; Age related macular degeneration; Anatomy; Area; Award; Back; Biological; Blindness; Cell Surface Receptors; Cell surface; Cells; Chronic; Clinical; Clinical Trials; Colorado; Committee Members; Communities; Development; Diabetes Mellitus; Diabetic Retinopathy; Diagnosis; Disease; Drug Delivery Systems; Drug Industry; Drug Kinetics; Emerging Technologies; Epidemic; Event; Eye; Eye diseases; Faculty; Failure; Feedback; Fees; Financial Support; Fire - disasters; Funding; Future; Gene Delivery; Generations; Glaucoma; Goals; Health; Individual; Industry; Inherited; Injection of therapeutic agent; Journals; Knowledge; Life Expectancy; Medical; Methods; MicroRNAs; Minority; Nanotechnology; Nucleic Acids; Ophthalmology; Oral; Paper; Participant; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Posterior eyeball segment structure; Proteins; Publications; Recruitment Activity; Research; Retinal; Retinal Diseases; Science; Scientist; Slide; Small Interfering RNA; Students; System; Therapeutic Agents; Tissues; Translational Research; Translations; Travel; Underrepresented Minority; United States National Institutes of Health; Universities; Vitreous humor; Water; Woman; abstracting; base; bench to bedside; career; experience; gene delivery system; gene therapy; inherited retinal degeneration; meetings; novel; novel strategies; novel therapeutics; nuclease; ophthalmic drug; posters; product development; ranibizumab; small molecule; socioeconomics; success; symposium; therapy development; waiver

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.

描述（由申请人提供）：视网膜疾病包括年龄相关性黄斑变性、糖尿病性视网膜病变、青光眼和遗传性视网膜世代是世界上失明的主要原因。随着预期寿命的增加和糖尿病流行的增加，视网膜疾病的社会经济负担预计是巨大的。视网膜疾病治疗开发中的限速步骤包括鉴定新的治疗剂以及将这些药剂递送至眼后部组织的新方法。随着新的治疗剂如siRNA、miRNA和基因疗法的鉴定，对开发新型递送系统的需求也在升级。几种核酸疗法可能由于缺乏合适的递送系统而失败，所述递送系统可以a）保护治疗剂免于被核酸酶降解，B）允许增强的细胞进入，c）使脱靶效应最小化，以及d）在治疗慢性视网膜病症中提供延长的递送。即使使用成功的蛋白质治疗剂如雷珠单抗，几年内频繁注射也可能对视网膜健康有害。这种限制可以通过开发蛋白质药物的长期递送方法来克服。对于小分子药物，无创递送到眼后部尚未成为临床现实。此外，即使通过侵入性方法，维持将小的水溶性分子递送到眼睛后部也是一个主要挑战。为了加快新的小分子，蛋白质和核酸治疗剂从实验室到床边的翻译，本次会议的目的是在不同的参与者群体中分享基于药品开发原则的前沿科学，包括来自学术界，工业界和监管机构的代表。预计观众将来自不同的个人群体，包括那些代表少数民族和传统上代表性不足的社区在科学事业。为期两天的会议将包括口头以及海报介绍。为这次会议提供的财政支持将有助于招募顶尖科学家和与会者。此外，还将提供登记费减免和旅费奖励，以鼓励少数群体和代表性不足的社区参与。根据会议上的报告和讨论，将在会议后3个月内编写一份白色论文，并及时提交眼科杂志发表。 公共卫生相关性：致盲性视网膜疾病具有重大的社会经济影响。将新的治疗剂从实验室推进到床边的限速步骤是递送到受影响的靶细胞。每一类治疗剂在开发临床上可用的递送系统中提出独特的问题。最近，基于siRNA的疗法可能由于其对细胞表面的脱靶效应而取得了有限的成功。这种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。为了加快新治疗药物的临床转化，本次会议的目的是介绍开发用于治疗眼后部疾病的新药物产品的尖端科学方法。