Development of a Peptide Therapy for Corneal Wound Healing

开发用于角膜伤口愈合的肽疗法

• 批准号: 10484711
• 负责人: Michael Flavin
• 金额: $ 30.09万
• 依托单位: VISO THERAPEUTICS INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10484711
• 关键词: Acceleration; Activities of Daily Living; Acute; Advanced Development; Affect; Americas; Amino Acids; Animal Model; Antibiotics; Area; Back; Blindness; Chemistry; Chicago; Clinical Trials; Contact Lenses; Cornea; Corneal Abrasion; Corneal Injury; Corneal Ulcer; Data; Defect; Derivation procedure; Development; Devices; Disease; Disease model; Dose; Emergency department visit; Epithelial; Eyedrops; Foreign Bodies; Formulation; Future; Goals; Illinois; Infection; Infection prevention; Inflammation; Injury; Intervention; Investigational Drugs; Investigational New Drug Application; Laboratories; Lead; Manufacturer Name; Membrane; Methods; Modeling; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Pain; Pathway interactions; Patients; Peptides; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Process; Production; Recovery; Research; Risk; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Standardization; Technology; Testing; Therapeutic; Time; Toxic effect; Toxicology; Trauma; Treatment Efficacy; Unemployment; United States Food and Drug Administration; Universities; Visual impairment; Work; base; chronic wound; clinically relevant; commercial application; commercialization; corneal epithelial wound healing; corneal epithelium; cost; drug development; effectiveness testing; efficacy testing; epithelial injury; epithelial wound; experience; experimental study; healing; histatin 5; histidine-rich proteins; in vivo Model; infection risk; innovation; model development; mouse model; novel; novel therapeutics; ocular surface; prevent; public health relevance; scale up; standard of care; success; translational model; treatment effect; wound; wound closure; wound healing

PROJECT SUMMARY/ABSTRACT Acute corneal epithelial injuries (corneal abrasions, foreign bodies, contact lens related injuries) are extremely common (more than 1 million per year). Injuries like corneal abrasions may lead to downstream consequences like corneal infections and inflammation, vision loss, and chronic wounds. Very limited interventions are currently available for these wounds. The standard of care for mild acute injuries is primarily supportive, with antibiotics given topically to prevent infectious complications. Severe cases may require ocular device placement, like amniotic membrane containing contact lenses, or even surgery. During the recovery time, patients suffer from pain, reduced vision and difficulty working and performing activities of daily living. The proposed work supports the development of a first-in-class, peptide-based, topical eye drop to accelerate the recovery time and allow patients to return to function sooner. This peptide therapy has a different mechanism of action than other eye drops given for ocular surface diseases. The objective of this Phase I STTR is to derisk the development of this novel therapy through two Aims (1) testing efficacy in in vivo models of disease and (2) determination of ideal parameters for drug application. The proposed research is innovative as it is the first study to investigate the use of these peptides in critical derisking drug development models. These studies are significant because they will advance the development of a new therapeutic through the use of rigorous and well-defined methods in clinically relevant translational models of disease and serve as the basis for later stages of development to bring this therapy to patients. Success will be determined by efficacy testing above a clinically relevant threshold for improvement and establishment of critical dosing parameters. Phase II follow on studies would include 28-day toxicological testing, formulation development, chemistry- manufacturing-control (CMC) studies and scale up of peptide production for subsequent clinical trials. The results of these experiments will support an Investigational New Drug (IND) application to the Food and Drug Administration (FDA).

项目概要/摘要 急性角膜上皮损伤（角膜擦伤、异物、隐形眼镜相关损伤）极其严重 常见（每年超过 100 万）。角膜擦伤等损伤可能会导致下游 后果如角膜感染和炎症、视力丧失和慢性伤口。非常有限 目前可以对这些伤口进行干预措施。轻度急性损伤的护理标准主要是 支持性治疗，局部给予抗生素以预防感染并发症。严重的情况可能需要 眼部装置植入，例如含有隐形眼镜的羊膜，甚至手术。期间 恢复时间长，患者会遭受疼痛、视力下降以及工作和执行活动困难 日常生活。拟议的工作支持开发一流的、基于肽的局部滴眼剂 加快康复时间，让患者更快恢复功能。这种肽疗法具有 与其他治疗眼表疾病的滴眼液相比，其作用机制不同。此举的目的 I 期 STTR 旨在通过两个目标（1）测试在中的疗效来消除这种新型疗法的开发风险 疾病的体内模型和（2）确定药物应用的理想参数。拟议的研究 具有创新性，因为这是第一项研究这些肽在关键降低风险药物开发中的用途 模型。这些研究意义重大，因为它们将通过以下方式促进新疗法的开发 在临床相关的疾病转化模型中使用严格且明确的方法，并作为 为后期开发阶段将该疗法带给患者奠定基础。成功取决于成效 测试高于临床相关阈值，以改善和建立关键剂量参数。 II 期后续研究将包括 28 天的毒理学测试、配方开发、化学- 生产控制（CMC）研究和扩大肽生产规模以用于后续临床试验。这 这些实验的结果将支持向食品和药物管理局申请研究性新药 (IND) 管理（FDA）。