A Clinical Trial of Antimicrobial Skin Substitutes for Treatment of Diabetic Ulce

描述（由申请人提供）：向美国国家糖尿病、消化和肾脏疾病研究所（NIDDK）提交的2型竞争性更新SBIR申请的目标是开展一项I/II期临床试验，以研究一种新型抗菌活人体皮肤替代品治疗危及生命的糖尿病并发症：慢性、不愈合的皮肤伤口的安全性和早期有效性。感染、未愈合的皮肤伤口是糖尿病患者发病率和死亡率的重要因素，也是糖尿病患者住院的主要原因。仅在美国，每年就有150万20岁以上的人被诊断出患有糖尿病。出院数据表明，在北美一年内住院的所有糖尿病患者中，有高达20%的人会经历无法愈合的皮肤伤口，通常局限于脚踝、脚和脚跟。不幸的是，在过去十年中，美国因糖尿病相关截肢而出院的人数有所上升，截至2006年，每年发生82,000例糖尿病引起的下肢截肢。对于糖尿病患者，截肢一侧肢体与对侧肢体预后不良相关，总体生存率降低。令人震惊的是，85%与糖尿病相关的下肢截肢的主要原因是感染、慢性、无法愈合的皮肤伤口。为了满足对治疗慢性不愈合皮肤伤口的创新治疗方法的迫切需求，Stratatech公司使用NIKS(R)细胞系生产了一种抗微生物的活体人体皮肤替代品。NIKS(R)细胞的一个独特特性是它们是长寿命的角质形成细胞祖细胞，并且是遗传均匀、非致瘤性、无病原体的人类细胞的一致来源。因为它们很容易通过使用非病毒载体进行基因改造，所以NIKS(R)角质形成细胞是体外基因改造方法的理想选择，可以创建具有增强抗菌能力的人类生物皮肤替代品。Stratatech战略性地专注于内源性宿主防御肽human cathelicidin (hCAP-18/ hl -37)，因为它对多种微生物、真菌和病毒具有抗菌活性，并且是先天防御伤口感染的关键组成部分。

DESCRIPTION (provided by applicant): The goal of this Type 2 Competitive Renewal SBIR application to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is to conduct a phase I/II clinical trial to investigate the safety and early efficacy of a novel antimicrobial living human skin substitute for the treatment of a life-threatening complication of diabetes: chronic, nonhealing skin wounds. Infected, nonhealing skin wounds contribute significantly to morbidity and mortality in individuals with diabetes mellitus and are a major reason for hospitalization of people with diabetes. In the United States alone, each year there are 1.5 million new cases of diabetes diagnosed in people aged 20 years or older. Hospital discharge data indicate that up to 20% of all diabetics hospitalized in North America within a given year will experience nonhealing skin wounds usually localized on ankles, feet, and heels. Unfortunately, the number of hospital discharges in the United States for diabetes-related amputations has risen in the last decade and as of 2006, 82,000 diabetes-induced lower extremity amputations occur each year. For the diabetic patient, amputation of one limb is associated with a poor prognosis for the contralateral limb, and a decreased rate of survival in general. An alarming 85% of diabetes-related lower extremity amputations have an infected, chronic, nonhealing skin wound as a primary causal factor. To address the critical need for innovative therapeutic approaches for treatment of chronic nonhealing skin wounds, Stratatech Corporation has used the NIKS(R) cell line to generate an antimicrobial living human skin substitute. A unique property of the NIKS(R) cells is that they are a long-lived keratinocyte progenitor and consistent source of genetically uniform, non-tumorigenic, pathogen-free human cells. Because they are readily amenable to genetic modification through the use of non-viral vectors, the NIKS(R) keratinocytes are ideal for ex vivo genetic modification approaches to create human biological skin substitutes with enhanced antimicrobial capabilities. Stratatech strategically focused on the endogenous host defense peptide human cathelicidin (hCAP-18/LL-37) because it exhibits antimicrobial activity against a broad range of microorganisms, fungi, and viruses and is a critical component of innate defenses against wound infection. PUBLIC HEALTH RELEVANCE: The goal of this project is to conduct a clinical trial to investigate the safety and early efficacy of a novel antimicrobial living human skin substitute for the treatment of a life- threatening complication of diabetes: chronic, nonhealing skin wounds. An alarming 85% of diabetes-related lower extremity amputations have an infected, chronic, nonhealing skin wound as a primary causal factor. To address the critical need for innovative therapeutic approaches for treatment of chronic nonhealing skin wounds, Stratatech Corporation has used the NIKS(R) cell line to generate an antimicrobial living human skin substitute. Stratatech strategically focused on the endogenous host defense peptide human cathelicidin (hCAP-18/LL-37) because it exhibits antimicrobial activity against a broad range of microorganisms, fungi, and viruses and is a critical component of innate defenses against wound infection.