Evaluation of ACT1 to Treat Diabetic Keratopathy

ACT1 治疗糖尿病角膜病的评价

• 批准号: 10910753
• 负责人: Elizabeth Ottinger
• 金额: $ 159.95万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10910753
• 关键词: Binding; Blindness; Burn injury; C-terminal; Cells; Clinical; Clinical Research; Clinical Trials; Collaborations; Connexin 43; Cornea; Corneal Injury; Defect; Development; Diabetes Mellitus; Disease; Epithelium; Ethanol; Evaluation; Extravasation; Fibrosis; Formulation; Granulation Tissue; Human; Immune; Individual; Injury; Keratopathy; Lead; Mediator; Morbidity - disease rate; Peptides; Pharmaceutical Preparations; Play; Pre-Clinical Model; Role; Safety; Signal Transduction; Therapeutic; Thinness; Toxicology; Treatment Protocols; Visual impairment; Work; conventional therapy; corneal burn; design; diabetic; diabetic rat; manufacture; research clinical testing; safety study; wound closure; wound healing

FirstStrings lead peptide, ACT1, is based on the C-terminal sequence of connexin43 (Cx43) and is designed to enter the cell and competitively inhibit the binding of endogenous Cx43. Cx43 plays critical roles in multiple aspects of wound healing, including spread of injury signals, extravasation of immune cells, granulation tissue formation, and fibrosis. Studies in preclinical models of efficacy show significant enhancement in corneal re-epithelialization and wound closure following ethanol-induced corneal burn injuries in diabetic rats, as compared with controls. This project will involve further development and safety studies of ACT1, a potential therapeutic compound for diabetic keratopathy. The BrIDGs team has completed PK/ADME and IND-directed toxicology studies, and developed and manufactured a clinical grade drug product, which the collaborators included in a successful IND application to initiate clinical trials. The BrIDGs team is conducting additional formulation and manufacturing work to support the ongoing clinical studies.

Firststrings Lead肽ACT1基于连接蛋白43（CX43）的C末端序列，旨在进入细胞并竞争性地抑制内源性CX43的结合。 CX43在伤口愈合的多个方面起着关键作用，包括损伤信号的扩散，免疫细胞的渗出，肉芽组织形成和纤维化。 与对照组相比，在功效临床前模型的研究表明，在乙醇引起的糖尿病大鼠角膜烧伤损伤后，角膜再上皮闭合和伤口闭合。该项目将涉及ACT1的进一步开发和安全研究，ACT1是一种潜在的糖尿病性角膜病治疗化合物。 BRIDGS团队已完成PK/ADME和指导毒理学研究，并开发和制造了临床级药物产品，合作者将其包括在成功的IND应用中，以启动临床试验。 Bridgs团队正在进行其他配方和制造工作，以支持正在进行的临床研究。