Development of a novel connexin-based peptide for the treatment of corneal injury

描述(申请人提供)：根据世界卫生组织的数据，全世界至少有1.71亿人患有糖尿病，到2030年，这一数字可能会翻一番以上。由于其慢性性质、并发症的严重性以及控制这些并发症所需的手段，不仅对所涉个人和家庭，而且对卫生系统来说，经济负担都是巨大的。糖尿病患者的创面愈合普遍严重受损，对社会经济和社会负担造成很大影响。糖尿病是20-74岁成年人新增失明病例的主要原因。虽然视网膜病变是导致这些患者失明的主要原因，但在过去的30年里，人们注意到47%-的糖尿病患者会出现糖尿病角膜病变或其他角膜异常，这些疾病可能会威胁视力。目前，治疗这些角膜上皮损伤的方法非常有限。FirstString Research，Inc.是一家早期生物技术公司，开发用于组织工程和再生医学应用的治疗性多肽。FirstString的领先的新型生物工程多肽ACT1基于连接蛋白43(Cx43)的C端序列，在调节细胞间通讯方面显示出巨大的前景。ACT1通过稳定缝隙连接和维持细胞间的通讯发挥作用，这是伤口修复或损伤反应所必需的。我们公司的初步数据表明，在糖尿病小鼠模型系统中，该肽可以加速伤口愈合，减少炎症反应，减少瘢痕形成，并恢复皮肤结构。此外，与对照多肽相比，ACT1多肽被证明能促进大鼠角膜乙醇烧伤后的角膜伤口愈合。基于这些早期的发现，我们假设ACT1肽将促进糖尿病大鼠角膜损伤后的角膜再上皮化和加速伤口闭合，正如本阶段SBIR应用中概述的目的所证明的那样。该项目中概述的目标的完成将为未来的第二阶段SBIR奠定基础，并可能导致在糖尿病角膜病变的临床管理中产生一种商业上可行的治疗方法。 与公共健康相关：根据世界卫生组织的数据，全球至少有1.71亿人患有糖尿病。糖尿病继发的角膜病变，如糖尿病角膜病变，是糖尿病相关发病率增加的原因，在糖尿病病程中影响47%-%的糖尿病患者。治疗这些角膜创伤的传统疗法已经失败。FirstStringResearch Inc.已经开发出一种新的治疗性多肽，可以促进角膜的再上皮化，减少疤痕和炎症，从而防止患有此类疾病的糖尿病患者潜在的失明。

DESCRIPTION (provided by applicant): According to the World Health Organization, at least 171 million people worldwide are living with diabetes and this figure is likely to more than double by the year 2030. Because of its chronic nature, the severity of its complications and the means required to control them, the economic burden is enormous not only to the individuals and families involved but also to the health system. Wound healing in diabetics, in general, is severely impaired, which has a great impact on the economic and social burden of our society. Diabetes is the leading cause of new cases of blindness among adults aged 20-74 years. Although retinopathy is the primary cause of blindness in these patients, in the past 3 decades it has been noted that 47-64% of diabetic patients will manifest diabetic keratopathy or other corneal abnormalities, which are potentially sight threatening. Currently, therapies to treat these corneal epithelial wounds are very limited. FirstString Research, Inc is an early stage biotech company developing therapeutic peptides for applications in tissue engineering and regenerative medicine. FirstString's lead novel bioengineered peptide dubbed ACT1, is based on the C-terminal sequence of connexin 43 (Cx43), and shows great promise in modulating intercellular communication. ACT1 works by stabilizing gap junctions and maintaining intercellular communication between cells that is essential for wound repair or injury response. Preliminary data from our company has indicated that this peptide can effect accelerated wound healing, reduce inflammatory response, reduce scar formation and restore skin structure following acute injury in a diabetic mouse model system. Furthermore, ACT1 peptide has been shown to promote corneal wound closure following ethanol burn injuries to the rat cornea, compared with that of a control peptide. Based on these early findings we hypothesize that ACT1 peptide will increase corneal re-epithelialization and accelerate wound closure following injury to the corneas of diabetic rats as demonstrated by the aims outlined in this Phase I SBIR application. The completion of aims outlined in this project will set the stage for a future Phase II SBIR and could lead to a commercially viable therapeutic in the clinical management of diabetic keratopathy. PUBLIC HEALTH RELEVANCE: According to the World Health Organization, at least 171 million people worldwide are living with diabetes. Corneal disorders secondary to diabetes, such as diabetic keratopathy, are an increasing cause of morbidity associated with diabetes and affects 47-64% of diabetics during the course of their disease. Conventional therapies for the treatment of these corneal wounds have failed. FirstString Research Inc. has developed a novel therapeutic peptide that may promote re-epithelialization of the cornea, reduce scarring and inflammation and thereby prevent potential blindness in diabetics with such disorders.