Evaluation of ACT1 to Treat Diabetic Keratopathy

FirstStrings前导肽ACT 1基于连接蛋白43（Cx43）的C末端序列，旨在进入细胞并竞争性抑制内源性Cx43的结合。Cx43在伤口愈合的多个方面发挥关键作用，包括损伤信号的传播、免疫细胞的外渗、肉芽组织形成和纤维化。 临床前有效性模型研究显示，与对照组相比，糖尿病大鼠乙醇诱导的角膜烧伤后，角膜上皮再生和伤口闭合显著增强。该项目将涉及ACT 1的进一步开发和安全性研究，ACT 1是一种潜在的糖尿病角膜病变治疗化合物。 BrIDGs团队已经完成了PK/ADME和IND指导的毒理学研究，并开发和制造了一种临床级药物产品，合作者将其纳入了成功的IND申请中，以启动临床试验。BrIDGs团队正在进行额外的配方和生产工作，以支持正在进行的临床研究。

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.