Noregen, a regenerative medicine ocular therapeutic

Noregen，一种再生医学眼部治疗药物

基本信息

批准号：
10599774
负责人：
Kimberly Drenser
金额：
$ 71.78万
依托单位：
RETINAL SOLUTIONS LLC
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10599774
关键词：
AXIN2 protein Ablation Address Affect Animal Model Area Biodistribution Biological Blindness Blood - brain barrier anatomy Blood Vessels Blood capillaries Businesses Clinical Trials Contracts Development Diabetic Retinopathy Disease Progression Dose Drops Drug Kinetics Edema Endothelial Cells Enzyme-Linked Immunosorbent Assay Escherichia coli Exclusion Exudate Eye Funding Gene Expression Goals Good Manufacturing Process Growth Growth Factor Half-Life Hour Human Hypoxia In Vitro Injections International Investigational Drugs Ischemia Knowledge Lasers Legal patent Marketing Measures Methods Modeling Molecular Weight Mus Natural regeneration Office Visits Oryctolagus cuniculus Outcome Oxygen Pathology Patients Persons Pharmaceutical Preparations Phase Process Qualifying Recombinants Regenerative Medicine Retina Retinal Detachment Retinal Diseases Retinal Vein Occlusion Running Safety Sampling Serum Signal Transduction Small Business Innovation Research Grant Stains Steroids Swelling Testing Therapeutic Time Toxicology United States Variant Vascular Endothelial Cell Vascular Endothelial Growth Factors Vascular Permeabilities Vision analytical method analytical ultracentrifugation beta catenin bevacizumab blocking factor commercial application dimer dosage endothelial stem cell in vivo in vivo Model innovation intravitreal injection light scattering liquid chromatography mass spectrometry manufacture mimetics monomer neovascularization neurovascular injury neurovascular unit novel therapeutics phase 1 study preservation regenerative therapy repaired response retina blood vessel structure retinal regeneration scale up sedimentation velocity sight restoration technological innovation therapeutic candidate vascular abnormality

项目摘要

ABSTRACT Ischemic retinopathies, such as diabetic retinopathy and retinal vein occlusion, are the leading cause of blindness in the United States. Common features are leaky vessels, swelling, capillary drop out, aberrant vessel growth and retinal detachment. Current treatments include laser ablation, anti-VEGFs and steroids. All are sub-optimal and only serve to slow disease progression and vision loss, and do not repair or regenerate the damaged vessels. Laser treatment is used to ablate avascular/ischemic regions of the retina to reduce the hypoxic drive which causes the abnormal vascular permeability, exudation and neovascularization. Anti-VEGFs and steroids transiently reduce vascular permeability but do not aid in normal retinal blood vessel repair or regeneration. However, the current product, Noregen (a norrin derived growth factor) restores vessel integrity and regenerates new non- fenestrated capillaries. Proof of principal was established in the most widely employed animal model for ischemic retinopathies, the mouse Oxygen Induced Retinopathy (OIR) model. In this Phase II project, we will optimize dosing of intravitreal injections, create and qualify analytical methods that will be used to establish product release criteria, and run preliminary pharmacokinetics studies to support an FDA IND submission. The long term goal of this project is to create a novel therapy for ischemic retinopathies that will restore the retina rather than simply slow pathology and vision loss.

抽象的缺血性视网膜病变，例如糖尿病性视网膜病变和视网膜静脉阻塞，是主要原因美国的失明情况。常见的特征是血管渗漏、肿胀、毛细血管脱落、异常血管生长和视网膜脱离。目前的治疗方法包括激光消融、抗 VEGF 和类固醇。所有这些都不是最佳的，只能减缓疾病进展和视力丧失，并且不会不修复或再生受损的血管。激光治疗用于消融无血管/缺血性病变视网膜区域以减少导致血管通透性异常的缺氧驱动，渗出和新生血管形成。抗 VEGF 药物和类固醇会暂时降低血管通透性但不帮助正常的视网膜血管修复或再生。然而，目前的产品， Noregen（一种 Norrin 衍生生长因子）可恢复血管完整性并再生新的非有孔毛细血管。在最广泛使用的动物模型中建立了本金证明对于缺血性视网膜病，小鼠氧诱导视网膜病（OIR）模型。在本次第二阶段项目中，我们将优化玻璃体内注射的剂量，创建并验证分析方法，这些方法将用于建立产品释放标准，并进行初步药代动力学研究以支持 FDA IND 提交。该项目的长期目标是创造一种新的缺血性治疗方法视网膜病变将恢复视网膜，而不仅仅是减缓病变和视力丧失。