A therapy for improving diabetic ulcer healing

改善糖尿病溃疡愈合的疗法

基本信息

批准号：
10820107
负责人：
SHEAU-YU Teddy HSU
金额：
$ 33.53万
依托单位：
ADEPTHERA, LLC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10820107
关键词：
Acceleration Acromegaly Adverse effects Affect Agonist American Amputation Animals Blood Circulation Blood Vessels Blood flow Chronic Circulation Complex Complications of Diabetes Mellitus Debridement Dermal Developed Countries Development Diabetes Mellitus Diabetic Foot Ulcer Disease model Endothelium Epithelium Etiology Exudate FDA approved Face Family Foot Ulcer Formulation Functional disorder Gel Half-Life Hormones Human Hyperglycemia Immune response Impairment In Situ Infection Injections Limb structure Lower Extremity Lymphangiogenesis Measures Mediating Melanocyte stimulating hormone Modeling Morbidity - disease rate Mus Nerve Neuroendocrine Tumors Patients Peptide Signal Sequences Peptides Peripheral Nervous System Diseases Persons Pharmacotherapy Play Prevalence RAMP1 Recurrence Regulation Risk Factors Rodent Role Series Signaling Protein Site Somatostatin Receptor Sterile coverings Streptozocin Therapeutic Uses Tissues Treatment Cost Vascular Permeabilities Vascularization Vasodilation absorption adrenomedullin analog angiogenesis calcitonin receptor-like receptor chronic ulcer chronic wound cost cost estimate db/db mouse diabetes management diabetic diabetic ulcer drug candidate endothelial dysfunction healing hemodynamics hormone therapy immune function improved in vivo ischemic injury limb amputation monomer mortality nanomedicine neurotransmission non-healing wounds novel novel therapeutics peptide drug pressure prevent receptor receptor-activity-modifying protein self assembly stem stem cells subcutaneous tissue regeneration vasculogenesis wound wound bed wound closure wound environment wound healing

项目摘要

Diabetic ulcer is one of the major complications of diabetes mellitus because of poor management of hyperglycemia. The prevalence of diabetic ulcer ranges from 14 to 24% among diabetes patients. In the U.S., diabetic ulcer affects over 900,000 peoples a year, and leads to >80,000 limb amputations annually. It was estimated that the management of diabetic ulcers represents over one third of the total cost of treatment of diabetes complications in developed countries. Current management of diabetic ulcers mainly focuses on the elimination of infection, the use of dressings to maintain a moist wound bed, offloading high pressure in the extremities, and debridement to improve healing. Although these measures have improved the survival of patients, there is a lack of pharmacotherapy that can substantially improve the healing of chronic wounds in diabetes patients. Clearly, novel therapeutics that can improve wound healing and prevent the recurrence of chronic ulcers in diabetes are much needed. Recent advance has shown that adrenomedullin family peptides play crucial roles in the regulation of vasculogenesis and immune response, and can protect against diabetes- associated etiology. These peptides have also been shown to accelerate wound healing, perhaps by improving angiogenesis, immune response, vascular permeability, and tissue regeneration in wound sites. Because these peptides have poor stability in vivo, they are poor drug candidates. To overcome this obstacle, we have developed a series of super-agonistic analogs that self-assemble to form gels in situ and slowly release the monomeric analog in vivo. Based on this discovery, we propose to develop an analog gel therapy for accelerating wound healing in diabetes patients by improving re-epithelialization, granulation, blood flow, and revascularization within the wound environment. In the proposed study, we will (1) identify an optimal gel formulation that provides sustained and localized treatment in vivo and (2) investigate the efficacy of the selected analog gel on wound healing in two rodent diabetic ulcer models. Successful development of this novel hormonal therapy has the potential to significantly reduce the mortality and morbidity resulting from nonhealing foot ulcers among diabetes patients.

糖尿病溃疡是糖尿病的主要并发症之一，由于糖尿病管理不善，导致糖尿病溃疡成为糖尿病的主要并发症之一。高血糖。糖尿病患者中糖尿病性溃疡的患病率为 14% 至 24%。在美国，糖尿病溃疡每年影响超过 900,000 人，每年导致超过 80,000 例截肢。原来是据估计，糖尿病溃疡的治疗费用占糖尿病治疗总费用的三分之一以上发达国家的糖尿病并发症。目前糖尿病溃疡的治疗主要集中在消除感染，使用敷料保持伤口床湿润，减轻伤口内的高压四肢和清创术以促进愈合。尽管这些措施改善了人们的生存对于患者来说，缺乏可以显着改善慢性伤口愈合的药物疗法糖尿病患者。显然，新疗法可以改善伤口愈合并防止复发糖尿病慢性溃疡是非常需要的。最近的进展表明，肾上腺髓质素家族肽在血管生成和免疫反应的调节中起着至关重要的作用，并且可以预防糖尿病相关病因。这些肽也被证明可以加速伤口愈合，也许是通过改善血管生成、免疫反应、血管通透性和伤口部位的组织再生。因为这些肽在体内稳定性差，是较差的候选药物。为了克服这个障碍，我们有开发了一系列超激动类似物，它们自组装形成原位凝胶并缓慢释放体内单体类似物。基于这一发现，我们建议开发一种类似凝胶疗法通过改善再上皮化、肉芽形成、血流和伤口愈合来加速糖尿病患者的伤口愈合伤口环境内的血运重建。在拟议的研究中，我们将 (1) 确定最佳凝胶提供持续和局部体内治疗的制剂，并且（2）研究该制剂的功效选择模拟凝胶对两种啮齿动物糖尿病溃疡模型的伤口愈合作用。本次开发成功新型激素疗法有可能显着降低因以下原因引起的死亡率和发病率：糖尿病患者的足部溃疡无法愈合。