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).

项目总结/摘要 急性角膜上皮损伤（角膜擦伤、异物、接触透镜相关损伤）是极其严重的。 常见（每年超过100万）。角膜擦伤等损伤可能导致下游 角膜感染和炎症、视力丧失和慢性伤口等后果。非常有限 目前对这些伤口进行了干预。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。严重病例可能需要 眼装置的放置，如含有羊膜的隐形眼镜，甚至手术。期间 恢复时间，患者遭受疼痛，视力下降，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肽基局部滴眼液 以加快恢复时间，让患者更快恢复功能。这种肽疗法具有 与治疗眼表疾病的其他滴眼剂的作用机制不同。的目的 I期STTR是通过两个目的来降低这种新疗法的发展风险：（1）测试在 疾病的体内模型和（2）药物应用的理想参数的确定。拟议研究 是创新的，因为这是第一项研究，调查使用这些肽在关键的去风险药物开发 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： 在疾病的临床相关转化模型中使用严格和明确定义的方法， 为后期的发展奠定基础，将这种疗法带给患者。成功与否取决于疗效 测试高于临床相关阈值，以改善和建立关键给药参数。 II期后续研究将包括28天毒理学试验、制剂开发、化学- 生产控制（CMC）研究和肽生产的规模扩大，用于随后的临床试验。的 这些实验的结果将支持向食品和药物管理局提交研究性新药（IND）申请。 管理局（FDA）。