Clinical Trial of Antimicrobial Skin to treat Diabetic Ulcers

描述(申请人提供)：向美国国家糖尿病与消化及肾脏疾病研究所(NIDDK)申请第二类竞争性更新SBIR的目的是进行一项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糖尿病危及生命的并发症--慢性、不可愈合的皮肤伤口--的安全性和早期疗效。感染的、无法愈合的皮肤伤口极大地增加了糖尿病患者的发病率和死亡率，也是糖尿病患者住院治疗的主要原因。仅在美国，每年就有150万名20岁或20岁以上的人被诊断为糖尿病。医院出院数据显示，在北美所有住院的糖尿病患者中，高达20%的人在一年内将经历通常位于脚踝、脚和脚后跟的无法愈合的皮肤伤口。不幸的是，美国因糖尿病相关截肢而出院的人数在过去十年里有所上升，截至2006年，每年发生8.2万例糖尿病导致的下肢截肢。对于糖尿病患者，一侧肢体截肢与对侧肢体预后差，总体存活率下降有关。令人担忧的是，85%的糖尿病相关下肢截肢手术的主要原因是感染的、慢性的、无法愈合的皮肤伤口。为了满足治疗慢性不可愈合皮肤创伤的创新治疗方法的迫切需要，Stratech公司使用NIKS(R)细胞系生产了一种抗菌活人体皮肤替代品。NIKS(R)细胞的一个独特特性是，它们是长寿的角质形成细胞前体，是遗传一致、无肿瘤、无病原体的人类细胞的始终如一的来源。由于NIKS(R)角质形成细胞很容易通过使用非病毒载体进行基因改造，因此是创造具有更强抗菌能力的人类生物皮肤替代品的体外基因改造方法的理想选择。Stratech的战略重点是内源性宿主防御肽人类长春花素(HCAP-18/LL-37)，因为它对广泛的微生物、真菌和病毒具有抗菌活性，是抵御伤口感染的天然防御系统的关键组成部分。

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.