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，包括与年龄相关的黄斑变性，糖尿病性视网膜病，青光眼和继承的视网膜世代是世界上失明的主要原因。随着预期寿命和糖尿病流行的增长，视网膜疾病的社会经济负担有望巨大。限制视网膜疾病治疗方法的限制步骤包括鉴定新的治疗剂以及将这些药物传递到眼后组织的新方法。通过鉴定新的治疗剂，例如siRNA，miRNA和基因疗法，需要开发新的递送系统的需求也会升级。由于缺乏适当的递送系统的可用性，可能会失败，a）可以保护治疗剂免受核酸酶降解的影响，b）b）允许增强的细胞进入，c）c）最小化脱靶效应，d）d）在治疗慢性视网膜疾病方面提供了长时间的递送。即使使用成功的蛋白质治疗剂，例如ranibizumab，几年来经常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递送方法，可以可能克服这种局限性。对于小分子药物，向眼睛的无创递送尚未成为临床现实。此外，即使通过侵入性方法，维持小型水溶性分子的递送也是一个重大挑战。为了加快新小分子，蛋白质和核酸治疗剂从长凳到床边的转换，本次会议的目的是基于药物产物开发原理共享尖端科学，包括来自学术界，工业，行业和监管机构的代表。预计观众将从一群不同的个人中吸引，包括代表少数群体和传统上代表性不足的科学职业社区的人。为期两天的会议将包括口头和海报演示。为此会议提供的财政支持将有助于招募顶级科学家和参与者。此外，还将提供注册费豁免和旅行奖，以鼓励少数群体和代表性不足的社区参与。根据会议上的演讲和讨论，会议结束后的3个月内将准备一份白皮书，并在《眼科期刊》上及时提交出版。 公共卫生相关性：视网膜疾病具有重大的社会经济影响。从长凳到床边推进新的治疗剂的速率限制步骤是传递到受影响的目标细胞。每类治疗剂在开发临床上可用的输送系统方面都构成了独特的问题。最近，由于siRNA的疗法对细胞表面的脱靶作用可能取得了有限的成功。这种治疗剂应进入细胞，同时避免与某些细胞表面受体的相互作用。为了加快新治疗剂的临床翻译，本次会议的目的是提出基于尖端的科学方法，用于开发新药品以治疗眼部疾病。