Restoration of Skin Structure and Function Post-Wounding

受伤后皮肤结构和功能的恢复

• 批准号: 7109950
• 负责人: ROBERT G GOURDIE
• 金额: $ 15.23万
• 依托单位: XEQUEL BIO, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7109950
• 关键词: injury; model; peptides; scars; skin; swine; wound healing

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.

描述（由申请人提供）：皮肤中的伤口修复过程在损伤后立即启动，并诱导一系列事件，包括炎症、增殖和瘢痕产生/组织重塑。伤口愈合的常见并发症之一是过度瘢痕形成，导致皮肤机械功能的不期望的变化以及美容性毁容。由疤痕形成引起的皮肤结构和功能的不利变化每年影响超过3500万美国公民，导致超过70亿美元的成本。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Robert Gourdie博士和Gautam Ghatnekar博士是一种新型生物工程肽的共同发明者，该肽有望在损伤后增强愈合和正常化皮肤外观和机械功能。最近的数据表明，差距连接蛋白连接蛋白43（Cx43）在协调皮肤中的伤口愈合中具有关键但不明确的作用。FSR肽基于Cx43的羧基末端片段，并已被合理设计为干扰Cx43相互作用蛋白的结合。小鼠中的初步数据表明，FSR的肽在皮肤机械创伤后的多个愈合阶段中具有有益效果，可能是通过放大内源性愈合机制。肽的作用包括减少初始炎症反应、加速愈合速度和减少瘢痕组织形成。此外，除了改善美容外观，FSR的肽促进受伤皮肤的再生和机械性能的正常化。在该STTR的I期，MUSC将根据FSR的分包合同在猪伤口愈合模型中进行我们的肽的“概念验证”和安全性研究，以确定在小鼠中观察到的临床有益效果是否在具有与人类更相似的愈合机制的动物模型中保持。在I期成功完成之前，我们未来II期的计划是在猪中进行GLP研究，作为I期临床试验的先决条件。FSR的总体目标是将其肽开发成药学上可接受的局部药剂，用于人类的手术和非手术皮肤伤口。