Topical Eyedrops Increasing Lysyl Oxidase Activity to Control Myopia

局部滴眼剂增加赖氨酰氧化酶活性来控制近视

• 批准号: 10603432
• 负责人: Sarah Abdulla Molokhia
• 金额: $ 34.5万
• 依托单位: IVEENA DELIVERY SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603432
• 关键词: Adolescent; Animal Experiments; Animal Model; Animals; Anti-Cholinergics; Atropine; Binding; Biochemical; Biological Markers; Biomechanics; Biometry; Blood; Cataract; Cavia; Chemicals; Childhood; Clinical; Collagen; Contact Lenses; Contralateral; Copper; Cornea; Country; Data; Data Analyses; Dimensions; Disease; Distant; Dose; Epidemic; Evaluation; Eye; Eye Development; Eyedrops; Eyeglasses; Formulation; Genetic Models; Glaucoma; Growth; Human; Ions; Label; Left; Length; Light; Link; Long-Term Effects; Mammals; Measurement; Mechanics; Modeling; Muscarinic Antagonists; Myopia; Open-Angle Glaucoma; Operative Surgical Procedures; Optics; Oryctolagus cuniculus; Pathologic; Perchlorates; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Pirenzepine; Prevalence; Primates; Progressive Myopia; Protein-Lysine 6-Oxidase; Refractive Errors; Retina; Retinal Degeneration; Retinal Detachment; Risk; Safety; Sclera; Small Business Innovation Research Grant; Structure; Technology; Testing; Tissues; Topical application; Toxic effect; Toxicology; Tupaiidae; Up-Regulation; Visual; Visual impairment; awake; cofactor; cost effective treatment; crosslink; cycloplegic; deprivation; design; economic impact; efficacy evaluation; emmetropization; experience; in vivo; irritation; lens; man; novel; ophthalmic examination; pharmacokinetic model; pharmacologic; response; retinal damage; safety assessment; safety study; safety testing; side effect; success; treatment duration; treatment effect; treatment strategy; trend

Project Summary Pediatric myopia, also known as nearsightedness, is an eye condition in which one is unable to bring distant objects into proper focus. It is the leading cause of vision impairment in the world. The estimated economic impact of uncorrected refractive error is estimated to be a loss of $202 billion of global gross domestic product. The prevalence of myopia and high myopia are increasing globally at an alarming rate, with significant increases in the risks for vision impairment from pathologic conditions associated with high myopia, including retinal damage, cataract and glaucoma. In 2000, the prevalence of myopia did not exceed 50% in any of the regions but, by 2050, the prevalence will be ≥ 50% in 57% of the countries, if current trends continue. We propose a novel topical eyedrop, IVMED-85, for treating myopia. It is a first in class medication that upregulates lysyl oxidase to pharmacologically induce scleral and corneal crosslinking and stiffening. Our central hypothesis is that the topical copper eyedrop treatment may enable a non-invasive, simple to use, and relatively cost-effective treatment for myopia by pharmacologically inducing scleral and corneal collagen crosslinking. We provide the first evidence that our proprietary IVMED-85 eyedrops induce biochemical crosslinking and biomechanical stiffening in cornea and sclera and reduced refraction and vitreous depth in guinea pig myopic model (Preliminary results). In this project, we will test safety of IVMED-85 in rabbits (Aim 1) and further elucidate efficacy and duration of effect after cessation in tree shrews, a para-primate model. Our plan is to achieve the feasibility results of safety and efficacy from this proposed Phase 1 project to plan for a Phase 2 SBIR assessing optimal duration in primates and GLP toxicology.

项目摘要 儿童近视，也被称为近视，是一种眼睛状况，其中一个是无法把遥远的 物体正确聚焦。它是世界上视力障碍的主要原因。估计经济 据估计，未矫正的屈光不正的影响是全球国内生产总值损失2020亿美元。 近视和高度近视的患病率在全球范围内正以惊人的速度增长， 在与高度近视相关的病理状况，包括视网膜病变， 白内障和青光眼。在2000年，任何一个地区的近视患病率都没有超过50 但是，如果目前的趋势继续下去，到2050年，57%的国家的患病率将≥ 50%。 我们提出了一种新的局部滴眼液，IVMED-85，用于治疗近视。这是一流的药物， 上调赖氨酰氧化酶，以诱导巩膜和角膜交联和硬化。 我们的中心假设是，局部铜滴眼液治疗可以实现一种非侵入性，简单易用， 通过诱导巩膜和角膜胶原蛋白植入治疗近视， 交联 我们提供了第一个证据，证明我们专有的IVMED-85滴眼液诱导生化交联， 豚鼠近视眼角膜和巩膜的生物力学硬化以及屈光度和玻璃体深度的降低 模型（初步结果）。在本项目中，我们将测试IVMED-85在家兔中的安全性（目的1），并进一步阐明 在树鼩（一种准灵长类动物模型）中停药后的疗效和作用持续时间。我们的计划是实现 该拟定I期项目的安全性和有效性的可行性结果，以计划II期SBIR评估 在灵长类动物和GLP毒理学中的最佳持续时间。