A new biomarker for diabetic foot ulcers

糖尿病足溃疡的新生物标志物

• 批准号: 8834521
• 负责人: Sufan Chien
• 金额: $ 28.07万
• 依托单位: NOVERATECH, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-09 至 2016-08-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8834521
• 关键词: Amputation; Animals; Biological Markers; Chronic; Collagen; Complications of Diabetes Mellitus; Country; Development; Diabetic Foot Ulcer; Diabetic ulcer; Diabetic wound; Functional disorder; Goals; Growth Factor; Healed; Human; Insulin-Dependent Diabetes Mellitus; Ischemia; Lower Extremity; Measures; Methodology; Modeling; National Institute of Diabetes and Digestive and Kidney Diseases; Neuropathy; Occupations; Oxygen; Pharmaceutical Preparations; Phase; Production; Recurrence; Research; Sterile coverings; Supplementation; Surrogate Endpoint; Testing; Tissues; Trauma; Ulcer; Up-Regulation; Vascular Endothelial Growth Factors; Wound Healing; angiogenesis; cost; cytokine; diabetic; diabetic patient; healing; inorganic phosphate; macrophage; pressure; public health relevance; response; wound

DESCRIPTION (provided by applicant): This proposal is submitted in response to the new NIDDK announcement (PA-14- 058) calling for development of methodologies or biomarkers to help understand the pathophysiology of T1D type 1 diabetes (T1D) complications. An estimated 15-25% of the 25.8 million diabetic patients in this country will develop diabetic foot ulcers (DFU) at some point in their lives. DFU is the leading cause of non-traumatic lower-extremity amputations caused by non-healing wounds. Despite thousands of dressing products developed to treat chronic wounds, none has proven effective for DFU. As stated in the RFA, a significant obstacle for progress in developing drugs for diabetic complications is the paucity of biomarkers and surrogate endpoints for measuring the initiation, progression, and response to treatments of diabetic complications. Although many factors are involved in non-healing DFU, tissue ischemia is known to be a major factor contributing to poor wound healing. Ischemia may not be the initiating factor for DFU, because most ulcers start from a combination of neuropathy, pressure loading, and/or trauma. However, tissue ischemia is the main cause that hinders healing. Providing oxygen to chronic ulcers has not obtained stable results. This is because oxygen is only one of the ingredients required for HEP production. The specific aim of this phase I proposal is to explore the possibility of using high- energy phosphate (HEP) contents as a biomarker to predict the progression and recurrence of diabetic ulcers. We plan to use a diabetic animal wound model, with and without ischemia, to test the changes of HEP in these wounds, along with the expression of several key factors known to be critical to wound healing, such as vascular endothelial growth factors, cytokines, macrophages, collagens, and angiogenesis, and correlated them to obtain a preliminary picture of the relationship between these factors and the haling of diabetic wounds. The result may provide a preliminary indication whether the change of HEP content alone, or along with other key factors, will be better used to predict the likelihood of healing. This is a difficult job, but we already have a proof-of-concept.

描述（由申请人提供）：本提案是为了响应新的NIDDK公告（PA-14- 058）而提交的，该公告呼吁开发方法或生物标志物，以帮助了解T1 D 1型糖尿病（T1 D）并发症的病理生理学。据估计，该国2580万糖尿病患者中有15-25%会在一生中的某个时候患上糖尿病足溃疡（DFU）。DFU是由不愈合伤口引起的非创伤性下肢截肢的主要原因。尽管开发了数千种用于治疗慢性伤口的敷料产品，但没有一种被证明对DFU有效。正如RFA中所述，糖尿病并发症药物开发进展的一个重大障碍是缺乏生物标志物和替代终点，用于测量糖尿病并发症的开始、进展和治疗反应。 虽然许多因素涉及不愈合DFU，但已知组织缺血是导致伤口愈合不良的主要因素。缺血可能不是DFU的起始因素，因为大多数溃疡都是由神经病变、压力负荷和/或创伤的组合引起的。然而，组织缺血是阻碍愈合的主要原因。为慢性溃疡提供氧气尚未获得稳定的结果。这是因为氧气只是HEP生产所需的成分之一。 该I期提案的具体目的是探索使用高能磷酸盐（HEP）含量作为生物标志物预测糖尿病溃疡进展和复发的可能性。我们计划使用糖尿病动物伤口模型，有和没有缺血，以测试这些伤口中的HEP的变化，沿着已知对伤口愈合至关重要的几个关键因子的表达，如血管内皮生长因子，细胞因子，巨噬细胞，胶原蛋白和血管生成，并将它们关联起来，以获得这些因子与糖尿病伤口haling之间关系的初步图像。该结果可以提供一个初步的指示，是否HEP含量的变化单独或沿着与其他关键因素，将更好地用于预测愈合的可能性。这是一项艰巨的工作，但我们已经有了一个概念验证。