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

新型连接蛋白肽治疗糖尿病伤口的评价

• 批准号: 8285078
• 负责人: Gautam Sudhir Ghatnekar
• 金额: $ 30万
• 依托单位: XEQUEL BIO, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8285078
• 关键词: Acute; Advanced Development; Adverse reactions; American; Amputation; Animals; Appearance; Autopsy; Becaplermin; Binding; Biomedical Engineering; Blood Vessels; Cells; Chronic; Clinical; Clinical Research; Clinical Trials; Comparative Study; Connexin 43; Connexins; Cost Savings; Development; Diabetes Mellitus; Diabetic Foot; Diabetic Foot Ulcer; Diabetic wound; Disease; Evaluation; Extravasation; Eye; Family member; Family suidae; Fibrosis; Foot Ulcer; Funding; Future; Gangrene; Gel; Genes; Granulation Tissue; Growth; Healed; Healthcare; Healthcare Systems; Heart Diseases; Hospitalization; Human; Immune; Impaired wound healing; In Situ Hybridization; Infection; Inflammation; Inflammatory; Injury; Investigational Drugs; Laboratory Research; Market Research; Measures; Mechanics; Medical center; Modeling; New Drug Approvals; Operative Surgical Procedures; Oryctolagus cuniculus; Patients; Pattern; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacotherapy; Phase; Plastic Surgical Procedures; Play; Proteins; Quality of life; Rattus; Redness; Research; Rodent; Role; Safety; Signal Pathway; Signal Transduction; Skin; Small Business Innovation Research Grant; Solutions; South Carolina; Technology; Time; Topical application; Toxic effect; Toxicokinetics; Ulcer; United States; Universities; Walking; Wound Healing; base; cost; db/db mouse; design; diabetic; diabetic patient; diabetic wound healing; efficacy evaluation; foot; good laboratory practice; healing; improved; insight; interest; intravenous administration; irritation; loved ones; man; middle age; mouse model; neutrophil; novel; pharmacokinetic characteristic; phase 2 study; pre-clinical; public health relevance; research and development; response; skin regeneration; treatment strategy; wound

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.

描述（由申请人提供）：根据美国糖尿病协会，美国有超过1600万人患有已知糖尿病。糖尿病患者通常表现出伤口愈合受损。大约20％的糖尿病患者会在其一生中出现足部溃疡。糖尿病足溃疡（DFU）代表了一个主要问题，可能会大大损害患者的生活质量，需要长时间住院，并且可能涉及感染，坏疽和截肢。据估计，对于每个新的脚溃疡，在头两年中，中年糖尿病患者的归因成本约为30,000美元。在美国，DFU对医疗保健系统的成本为每年超过10亿美元。关于为什么糖尿病伤很难治愈的一个很好的理由是，它们不会在正常的愈合阶段进展。取而代之的是，人们认为糖尿病伤被捕获并被困在伤口愈合的最初炎症阶段。 Firststring Research，Inc。（FSR）是位于南卡罗来纳州查尔斯顿的一家生物技术公司。 FSR的创始人，博士。 Robert Gourdie和Gautam Ghatnekar是一类新型生物工程肽的CO发明者 - 我们称为ACT肽。第一阶段资助的研究在糖尿病C57BL/KSJ-M+/+LeptDB（DB+/DB+）小鼠模型中为ACT1肽在治疗糖尿病伤口治疗的功效和潜力提供了有力的证据。肽会影响明显更快的闭合速率。在ACT1治疗的伤口中，主观参数（例如发红和整体外观）也得到了显着改善。 ACT1肽在我们的I期SBIR研究中没有显示出任何不良反应或安全性问题，该研究通过完整的死灵病和组织病理学评估进行了评估。此外，为了增强我们理解和预测与ACT1PEPTIDE的安全性和功效相关的问题的能力，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。特别令人感兴趣的是血管生成信号传导引起的变化，这些变化为用ACT1肽治疗的伤口中皮肤血管模式的再生提供了基本的机械洞察力。我们的市场研究表明，目前的糖尿病和慢性伤口伤口愈合的疗法和药物总体上是症状，经验，不可预测的，并且在很大程度上是无效的。我们的ACT1肽可能会提供基于机械的解决方案，不仅可以更快地闭合伤口，还可以节省大量成本，更重要的是改善了糖尿病患者的生活质量。在此II阶段的应用中，宾夕法尼亚州立大学的好时医学中心，宾夕法尼亚州赫尔希医学中心，伤口愈合研究实验室主任Paul Ehrlich博士和北卡罗来纳州达勒姆市Biomarck Pharmaceuticals的Indu Parikh博士已同意协助我们实现我们的目标。 公共卫生相关性：糖尿病是一种令人衰弱的状况，不仅威胁着患有疾病的人们的生活质量，而且威胁着家人和亲人。大约20％的糖尿病患者在其一生中会出现脚踏性溃疡，并且表现出伤口愈合受损。一般而言，糖尿病或慢性伤口治愈不佳的一个很好的原因是它们在炎症阶段被“卡住”。这项技术为减少炎症和更快的糖尿病伤口治愈提供了希望，从而改善了生活质量并节省了数百万美元的与医疗保健相关的成本。