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

开发用于治疗角膜损伤的新型连接蛋白肽

• 批准号: 8198936
• 负责人: Gautam Sudhir Ghatnekar
• 金额: $ 23.28万
• 依托单位: XEQUEL BIO, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8198936
• 关键词: Acute; Adult; Affect; Animals; Appearance; Binding; Biological Assay; Biological Models; Biomedical Engineering; Blindness; Budgets; Burn injury; C-terminal; Cells; Chemicals; Chronic; Cicatrix; Clinical; Clinical Management; Connexin 43; Connexins; Cornea; Corneal Diseases; Corneal Injury; Corneal Ulcer; Data; Development; Diabetes Mellitus; Diabetic mouse; Disease; Drug Formulations; Economic Burden; Economics; Epithelial Cells; Esthesia; Ethanol; Event; Extravasation; Eyedrops; Family; Fibrosis; Funding; Future; Gap Junctions; Granulation Tissue; Healed; Health Care Costs; Health system; Healthcare; Immune; In Vitro; Individual; Inflammation; Inflammatory Response; Injury; Keratopathy; Lead; Life; Maintenance; Mechanics; Minor; Morbidity - disease rate; Naltrexone; Narcotic Antagonists; Nature; Patients; Peptides; Phase; Play; Predisposition; Prevalence; Process; Proteins; Rattus; Redness; Regenerative Medicine; Research; Retina; Retinal Diseases; Role; Secondary to; Series; Severities; Signal Transduction; Skin; Small Business Innovation Research Grant; Societies; South Carolina; Staging; Streptozocin; Structure; Therapeutic; Tissue Engineering; Toxic effect; Trauma; United States National Institutes of Health; Vascularization; Vision; Visual; Wistar Rats; Work; World Health Organization; Wound Healing; Wounds and Injuries; aged; base; comparative efficacy; conventional therapy; corneal epithelium; db/db mouse; design; diabetic; diabetic patient; diabetic rat; healing; improved; intercellular communication; lens; migration; mouse model; novel; novel therapeutics; pre-clinical; prevent; repaired; response; response to injury; safety study; social; type I diabetic; wound

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.

描述（由申请人提供）：根据世界卫生组织的说法，全世界至少有1.71亿人患有糖尿病，到2030年，这个数字可能会增加一倍以上。由于其慢性性质，其复杂性的严重性和控制它们所需的手段，经济负担不仅对个人和家庭涉及健康系统。通常，糖尿病患者的伤口愈合受到严重损害，这对我们社会的经济和社会负担产生了重大影响。糖尿病是20-74岁成年人丧失新病例的主要原因。尽管视网膜病是这些患者失明的主要原因，但在过去的三十年中，人们注意到，有47-64％的糖尿病患者会表现出糖尿病性角膜病或其他角膜异常，这可能会危及视力的威胁。目前，治疗这些角膜上皮伤口的疗法非常有限。 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肽。 FirstString的主要小说生物工程肽（称为ACT1）基于连接蛋白43（CX43）的C末端序列，并在调节细胞间通信方面显示出巨大的希望。 ACT1通过稳定间隙连接并维持细胞之间的细胞间通信作用，这对于伤口修复或损伤反应至关重要。我们公司的初步数据表明，这种肽可以在糖尿病小鼠模型系统中急性损伤后影响加速伤口愈合，减少炎症反应，减少疤痕形成并恢复皮肤结构。此外，与对照肽相比，ACT1肽已被证明可促进大鼠角膜的乙醇烧伤后角膜伤口闭合。基于这些早期发现，我们假设ACT1肽将增加角膜上皮上皮化，并加速糖尿病大鼠角膜损伤后的伤口闭合，如本I阶段I SBIR应用中所概述的目的所示。该项目中概述的目标的完成将为未来的II期SBIR奠定基础，并可能导致在糖尿病性角膜病的临床管理中获得商业可行的治疗性。 公共卫生相关性：根据世界卫生组织的说法，全球至少有1.71亿人患有糖尿病。角膜疾病继发于糖尿病，例如糖尿病性角膜病，是与糖尿病相关的发病率的越来越多的原因，在疾病过程中影响了47-64％的糖尿病患者。这些角膜伤口治疗的常规疗法失败了。 Firststring Research Inc.开发了一种新型的治疗肽，可以促进角膜的重新上皮化，减少疤痕和炎症，从而防止患有这种疾病的糖尿病患者潜在的失明。