Evaluation Of A Novel Connexin-Based Peptide For The Treatment Of Diabetic Wounds

描述（由申请人提供）：根据美国糖尿病协会，在美国有超过1600万人患有已知的糖尿病。糖尿病患者通常表现出受损的伤口愈合。大约20%的糖尿病患者在其一生中会发生足部溃疡。糖尿病足溃疡（DFU）是一个严重的问题，它会严重损害患者的生活质量，需要长期住院治疗，并可能涉及感染、坏疽和截肢。据估计，对于每一个新的足部溃疡，中年糖尿病男性在头两年的可归因成本约为30，000美元。在美国，DFU对医疗保健系统的成本每年超过10亿美元。糖尿病伤口坚韧愈合的一个公认的原因是它们不能通过正常的愈合阶段。相反，人们认为糖尿病伤口被捕获并保持在伤口愈合的初始炎症阶段。FirstString Research，Inc. (FSR)是一家位于南卡罗来纳州查尔斯顿的生物技术公司。FSR的创始人Robert Gourdie博士和Gautam Ghatnekar博士是一类新型生物工程肽的共同发明者-我们称之为ACT肽。在糖尿病C57 BL/KsJ-m+/+Leptdb（db+/db+）小鼠模型中进行的I期资助的研究为ACT 1肽在治疗糖尿病伤口中的功效和潜力提供了强有力的证据。该肽实现显著更快的闭合速率。ACT 1治疗伤口的主观参数（如发红和整体外观）也得到了显著改善。在我们的I期SBIR研究中，ACT 1肽未显示任何不良反应或安全性问题，如通过完整的尸检和组织病理学评价所评价的。此外，为了提高我们理解和预测与ACT 1肽的安全性和有效性相关的问题的能力，我们还将使用基因微阵列和计算方法来分析对伤口愈合中涉及的关键信号通路的影响。特别感兴趣的是血管生成信号传导中诱导的变化，其提供了对用ACT 1肽治疗的伤口中皮肤血管模式再生的基本机制性见解。我们的市场研究表明，目前用于糖尿病和慢性伤口愈合的疗法和药物通常主要是症状性的、经验性的、不可预测的，并且在很大程度上是无效的。我们的ACT 1肽可能提供一种基于机械的解决方案，不仅可以更快地闭合伤口，还可以显著节省成本，更重要的是提高糖尿病患者的生活质量。在本II期申请中，宾夕法尼亚州立大学好时医疗中心外科整形外科部伤口愈合研究实验室主任Paul埃利希博士和北卡罗来纳州达勒姆BioMarck Pharmaceuticals总裁兼CSO Indu Parikh博士同意协助我们实现目标。 公共卫生相关性：糖尿病是一种使人衰弱的疾病，不仅威胁着患有这种疾病的人的生活质量，而且还威胁着家庭成员和亲人的生活质量。大约20%的糖尿病患者在其一生中会发生足部溃疡，并且他们表现出伤口愈合受损。糖尿病或慢性伤口愈合不良的一个公认的原因通常是它们“停留”在炎症阶段。这项技术为减少炎症和更快地愈合糖尿病伤口提供了希望，从而提高了生活质量，节省了数百万美元的医疗保健相关费用。

DESCRIPTION (provided by applicant): According to the American Diabetes Association, there are more than 16 million people in the United States with known diabetes. Diabetic patients commonly demonstrate impaired wound healing. Approximately 20 percent of patients with diabetes will develop foot ulceration in their lifetime. Diabetic foot ulceration (DFU) represents a major problem that can significantly impair the patient's quality of life, require prolonged hospitalization, and may involve infection, gangrene, and amputation. It has been estimated that for each new foot ulcer the attributable cost for a middle-aged diabetic man in the first two years is approximately $ 30,000. The cost of DFU to the healthcare system is over one billion dollars per year in the United States. A well- established reason as to why diabetic wounds are tough to heal is that they do not progress through the normal healing phases. Instead, it is thought that diabetic wounds are caught and remain trapped in the initial inflammatory phase of wound healing. FirstString Research, Inc. (FSR) is a biotech company located in Charleston, South Carolina. The founders of FSR, Drs. Robert Gourdie and Gautam Ghatnekar are co inventors of a class of novel bioengineered peptides - we refer to as ACT peptides. Phase I funded studies in the diabetic C57BL/KsJ-m+/+Leptdb (db+/db+) mouse model have provided strong evidence for efficacy and potential of the ACT1 peptide in the treatment of diabetic wounds. The peptide effects a significantly faster closure rate. Subjective parameters such as redness and overall appearance were also substantially improved in ACT1 treated wounds. ACT1 peptide did not show any adverse reactions or safety concerns in our Phase I SBIR studies, as evaluated by a complete necropsy and histopathological evaluation. Moreover, to enhance our ability to understand and anticipate issues associated with the safety and efficacy of ACT1peptide, we will also use gene microarray and computational approaches to analyze effects on key signaling pathways involved in wound healing. Of particular interest will be changes induced in angiogenic signaling that provide basic mechanistic insight into the regeneration of skin vascular pattern in wounds treated with ACT1 peptide. Our market research has indicated that present therapies and drugs for wound healing in diabetes and chronic wounds in general are predominantly symptomatic, empirical, unpredictable, and largely ineffective. Our ACT1 peptide potentially offers a mechanistically based solution to not just faster wound closure but also significant cost savings and more importantly improving the quality of life in diabetic patients. In this Phase II application, Dr. Paul Ehrlich, Director for the Wound Healing Research Laboratory in the Division of Plastic Surgery, Department of Surgery, Hershey Medical Center at Penn State University and Dr. Indu Parikh, President and CSO, BioMarck Pharmaceuticals, Durham, NC have agreed to assist us in achieving our aims. PUBLIC HEALTH RELEVANCE: Diabetes is a debilitating condition that threatens the quality of life of not just the people suffering from the disease but also family members and loved ones. Approximately 20 percent of patients with diabetes develop foot ulceration in their lifetime and they demonstrate impaired wound healing. A well-accepted reason for the poor healing of the diabetic or chronic wounds in general is that they are 'stuck' in the inflammatory phase. This technology provides promise for reduced inflammation and faster healing of diabetic wounds thereby improving the quality of life and saving millions of dollars in health care related costs.