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

描述（由申请人提供）：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，这一数字可能会增加一倍以上。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，不仅对有关个人和家庭，而且对卫生系统来说，经济负担都是巨大的。一般来说，糖尿病患者的伤口愈合严重受损，这对我们社会的经济和社会负担产生了很大的影响。糖尿病是20-74岁成年人失明新病例的主要原因。虽然视网膜病变是这些患者失明的主要原因，但在过去的30年里，有47-64%的糖尿病患者会出现糖尿病性角膜病变或其他角膜异常，这是潜在的视力威胁。目前，治疗这些角膜上皮性伤口的方法非常有限。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的治疗性肽。FirstString的新型生物工程肽ACT1是基于连接蛋白43 （Cx43）的c端序列，在调节细胞间通讯方面显示出很大的前景。ACT1通过稳定间隙连接和维持细胞间的通讯起作用，这对伤口修复或损伤反应至关重要。我们公司的初步数据表明，在糖尿病小鼠模型系统中，这种肽可以加速伤口愈合，减少炎症反应，减少疤痕形成，恢复急性损伤后的皮肤结构。此外，与对照肽相比，ACT1肽已被证明能促进乙醇烧伤后大鼠角膜伤口愈合。基于这些早期发现，我们假设ACT1肽会增加糖尿病大鼠角膜损伤后的角膜再上皮化和加速伤口愈合，正如本I期SBIR应用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II期SBIR奠定基础，并可能导致糖尿病角膜病变临床管理中商业上可行的治疗方法。

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.