Novel Antiangiogenic Peptides for Treatment of Exudative AMD

用于治疗渗出性 AMD 的新型抗血管生成肽

基本信息

批准号：
8415053
负责人：
NADER SHEIBANI
金额：
$ 124.35万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-03-01 至 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8415053
关键词：
Adverse effects Age Age related macular degeneration American Amino Acids Angiogenesis Inhibitors Animal Model Animals Apoptosis Apoptotic Attenuated Avastin Basic Science Benchmarking Biomedical Engineering Blindness Blood Vessels Bypass Charge Chemicals Chemistry Choroid Choroidal Neovascularization Chronic Clinical Clinical Research Collaborations Cyclic GMP Development Disease Disease Progression Dose Drug Delivery Systems Drug Formulations Epithelial Event Exudative age-related macular degeneration Eye Frequencies Genetic Transcription Goals Growth Half-Life Human Hydrolysis Image Imaging technology In Vitro Injectable Injection of therapeutic agent Institutes Label Lasers Lead Life Light Longitudinal Studies Lucentis Marketing Modeling Molecular Mimicry Monoclonal Antibody R24 Mus NanoGel National Eye Institute Nebraska Neurons Ophthalmology Parents Pathogenesis Pediatrics Peptides Pharmaceutical Preparations Phase Phase I Clinical Trials Photochemotherapy Physiological Pigments Polymers Process Prodrugs Production Proteins Regimen Research Personnel Retinal Retinal Diseases Rodent Safety Schedule Signal Transduction Testing Thrombospondin 1 Toxic effect Toxicology Translating Translational Research Treatment Protocols Universities Urology Variant Vascular Endothelial Growth Factors Vision Disorders Wisconsin angiogenesis aqueous base blocking factor design drug development effective therapy efficacy testing improved in vivo inhibitor/antagonist mimetics mimicry nanoformulation nanomedicine neovascular neovascularization new growth novel ocular angiogenesis ocular neovascularization pre-clinical prevent programs public health relevance research study residence safety testing screening tumor growth

项目摘要

DESCRIPTION (provided by applicant): An interdisciplinary consortium of investigators from the Departments of Ophthalmology and Pediatrics at the University of Wisconsin in collaboration with the Northwestern University Chemistry of Life Processes Institute, Biomedical Engineering, Urology, and Pediatrics, and the University of Nebraska Center for Drug Delivery and Nanomedicine, proposes to increase the pace at which basic science discoveries on disease mechanisms can be translated into therapies for exudative age-related macular degeneration (AMD), a stated goal of the R24 National Eye Institute Translational Research Program on Therapy for Visual Disorders. This scientific partnership will employ its diverse scientific expertise to characterize and test potential therapies for exudative AMD in animal models by using a combination of cutting-edge physiological, chemical, analytical and imaging approaches. By screening novel peptides derived from endogenous inhibitors of angiogenesis for their ability to prevent neovascularization in animal models that mimic AMD, we will accelerate drug development before testing in humans. Improving drug delivery to the eye as an integral part of these experiments will also be a high priority. Specific goals of this project are to: (1) determin whether the peptide mechanisms of action in the eye are through their mimicry of these natural inhibitors; (2) Produce and identify optimal new derivatives of benchmark peptides best suited to intravitreal treatment of AMD, where these are ranked by efficacy in CNV models, individually and in combination; (3) Select and tested the most active peptide(s) and their most slowly cleared formulations for efficacy in AMD models. The best candidate(s) will undergo GLP production and then safety testing, including retinal safety to select a suitable new peptide-based entity for clinical development; and (4) Establish preclinical basis for ultimate human treatment protocol for this entity through animal models of retinal disease examined via state-of-the art in vivo retinal imaging and histopathological analysis. Ultimately, the experimental result of these interrelated aims will guide us in developing more successful therapies for those afflicted by currently incurable blinding diseases with a neovascular component.

描述（由申请人提供）：威斯康星大学科学和儿科系的研究人员的跨学科联盟与西北大学生命过程化学研究所，生物医学工程，泌尿外科，泌尿外科，泌尿外科和儿科，以及Nebrask的疾病中的疾病中心，以提高疾病的疾病中心，以提高纽约尼诺胺的疾病中心，以提高疾病的疾病中心，以提高nanomecice sodices offics office nanomecic offic，被翻译成渗出性年龄相关的黄斑变性（AMD）的疗法，这是R24国家眼科研究所的视觉疾病治疗研究计划的既定目标。这种科学合作伙伴关系将利用其多样化的科学专业知识来表征和测试动物模型中渗出性AMD的潜在疗法，通过使用尖端的生理，化学，化学，分析和成像方法的结合。通过筛选源自血管生成的内源性抑制剂的新肽，以防止模仿AMD的动物模型中的新血管形成，我们将在人类进行测试之前加速药物发育。作为这些实验不可或缺的一部分，将药物输送到眼睛的一部分也将是一个高优先级。该项目的具体目标是：（1）确定眼睛中作用的肽机制是否是通过模仿这些天然抑制剂的；（2）生产和确定最适合于AMD玻璃体内治疗的基准肽的最佳新衍生物，其中这些肽是单独和组合在CNV模型中通过功效对其进行排名的；（3）在AMD模型中选择并测试了最活跃的肽及其最缓慢清除的配方。最佳候选人将接受GLP的生产，然后进行安全测试，包括视网膜安全，以选择合适的基于肽的新实体进行临床开发；（4）通过通过体内视网膜成像和组织病理学分析研究的视网膜疾病模型和组织病理学分析来为该实体建立临床前的基础。最终，这些相互关联的目标的实验结果将指导我们为患有新血管成分的目前无法治愈的盲目疾病而开发更成功的疗法。