Restoration of Skin Structure and Function Post-Wounding

描述（由申请人提供）：皮肤伤口修复过程在受伤后立即启动，并诱导一系列事件，包括炎症、增殖和疤痕产生/组织重塑。1 .伤口愈合的常见并发症是疤痕过多，导致皮肤机械功能的不良变化，以及美容毁容。疤痕形成导致的皮肤结构和功能的不良变化每年影响超过3500万美国公民，造成的损失超过70亿美元。FirstString Research, LLC （FSR）是一家位于南卡罗来纳州查尔斯顿的生物技术初创公司。FSR的创始人，dr。Robert Gourdie和Gautam Ghatnekar是一种新型生物工程肽的共同发明者，这种肽有望在损伤后促进愈合和恢复皮肤外观和机械功能。最近的数据表明，缝隙连接蛋白Connexin43 （Cx43）在协调皮肤伤口愈合中具有关键的作用，尽管尚未明确。FSR肽基于Cx43的羧基末端片段，被合理设计用于干扰与Cx43相互作用的蛋白的结合。小鼠的初步数据表明，FSR肽在皮肤机械损伤后的多个愈合阶段都有有益的作用，可能是通过放大内源性愈合机制。肽效应包括减少初始炎症反应，加速愈合速度和减少疤痕组织形成。此外，除了改善美容外观外，FSR的肽还能促进受伤皮肤的再生和机械性能的正常化。在该STTR的第一阶段，根据FSR的分包合同，我们的肽在猪伤口愈合模型中的“概念验证”和安全性研究将在MUSC进行，以确定在小鼠中观察到的临床有益效果是否适用于具有更类似于人类愈合机制的动物模型。在第一阶段成功完成之前，我们对未来第二阶段的计划是在猪身上进行GLP研究，作为第一阶段临床试验的先决条件。FSR的总体目标是将其肽开发成一种药学上可接受的局部剂，用于人类手术和非手术皮肤伤口。

DESCRIPTION (provided by applicant): The wound repair process in skin is initiated immediately after an injury and induces a cascade of events including inflammation, proliferation, and scar production/tissue remodeling. 1 of the common complications of wound healing is excessive scarring, leading to undesirable changes in skin mechanical function, as well as cosmetic disfiguration. The adverse changes in skin structure and function resulting from scar formation affects over 35 million US citizens a year resulting in costs of more than $7 billion dollars. FirstString Research, LLC (FSR) is a biotech startup company located in Charleston, South Carolina. The founders of FSR, Drs. Robert Gourdie and Gautam Ghatnekar are co inventors of a novel bioengineered peptide that shows promise in enhancing healing and normalizing skin appearance and mechanical function following injury. Recent data indicates that the gap junction protein Connexin43 (Cx43) has key, though ill- defined roles in orchestrating wound healing in skin. The FSR peptide is based on a carboxy-terminal fragment of Cx43 and has been rationally designed to interfere with the binding of Cx43-interacting proteins. Preliminary data in mouse indicate that FSR's peptide has beneficial effects in multiple phases of healing following mechanical wounding of skin, possibly via amplifying an endogenous healing mechanism. The peptide effects include reduction in initial inflammatory response, acceleration of healing rate and reduction in scar tissue formation. Moreover, in addition to improving cosmetic appearance, FSR's peptide promotes regeneration and normalization of the mechanical properties of wounded skin. In Phase I of this STTR, a "proof of concept" and safety study of our peptide in a pig model of wound healing will be undertaken at MUSC under a sub-contract from FSR to determine whether the clinically beneficial effects observed in mouse hold up in an animal model with healing mechanisms more comparable to humans. Pending successful completion of Phase I, our plan for a future Phase II, would be to undertake GLP studies in pigs as a pre-requisite for phase I clinical trials. It is FSR's overall objective to develop its peptide into a pharmaceutically acceptable topical agent for application to surgical and non-surgical skin wounds in humans.