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.

项目概要 小儿近视，也称为近视，是一种无法看清远处的眼睛疾病。 物体进入适当的焦点。它是世界上视力障碍的主要原因。预计经济 据估计，未矫正的屈光不正造成全球国内生产总值损失 2,020 亿美元。 全球范围内近视和高度近视的患病率正在以惊人的速度增长，且增幅显着 与高度近视相关的病理状况（包括视网膜）导致视力损害的风险 损伤、白内障和青光眼。 2000年，任何地区近视患病率均未超过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%。 我们提出了一种新型外用滴眼剂 IVMED-85，用于治疗近视。这是一流的药物 上调赖氨酰氧化酶，以药理学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能会实现一种非侵入性、易于使用、 通过药物诱导巩膜和角膜胶原蛋白治疗近视相对具有成本效益 交联。 我们提供了第一个证据，证明我们专有的 IVMED-85 滴眼剂可诱导生化交联和 豚鼠近视眼角膜和巩膜生物力学硬化以及屈光度和玻璃体深度降低 模型（初步结果）。在这个项目中，我们将测试 IVMED-85 在兔子身上的安全性（目标 1）并进一步阐明 树鼩（一种副灵长类动物模型）的功效和停止后的效果持续时间。我们的计划是实现 拟定第 1 阶段项目的安全性和有效性的可行性结果，以规划第 2 阶段 SBIR 评估 灵长类动物和 GLP 毒理学的最佳持续时间。