Novel peptide for enhancing diabetic wound healing

促进糖尿病伤口愈合的新型肽

基本信息

批准号：
10517746
负责人：
Chia Soo
金额：
$ 77.65万
依托单位：
SCARLESS LABORATORIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-24 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10517746
关键词：
Acceleration Adverse effects Affect Allografting American Amputation Anatomy Animal Model Animals Area Becaplermin Biological Blood Glucose Blood Vessels California Cause of Death Cell physiology Cells Cessation of life Chronic Cicatrix Clinic Clinical Clinical Research Clinical Sciences Clinical Trials Data Debridement Defect Development Diabetes Mellitus Diagnosis Dose Endothelial Cells Ensure Epidemic Epithelium Extracellular Matrix Family suidae Female Fibroblasts Formulation Funding Goals Good Manufacturing Process Grant Granulation Tissue Growth Factor Histologic Human Immunity Immunologic Deficiency Syndromes Impaired wound healing Impairment In Vitro Incidence Incubators Infection Infiltration Infrastructure Injury Link Metabolic Diseases Methods Microvascular Dysfunction Molecular Morbidity - disease rate Mus Myofibroblast Non-Insulin-Dependent Diabetes Mellitus Outcome Outcome Measure Patients Peptides Perfusion Peripheral Nervous System Diseases Pharmaceutical Preparations Phase Phase I/II Clinical Trial Physiological Population Prediabetes syndrome Predisposition Privatization Production Public Health Quality of life Recurrence Regimen Research Resources Rodent Model Safety Skin Skin repair Small Business Innovation Research Grant Small Business Technology Transfer Research Source Sterile coverings Testing Therapeutic Time Tissues Translational Research United States Food and Drug Administration United States National Institutes of Health Vascularization Work acute wound angiogenesis antimicrobial blood glucose regulation cell motility chronic ulcer chronic wound commercialization cost diabetic diabetic patient diabetic ulcer diabetic wound healing fetal fibromodulin first-in-human improved infection risk innovative technologies insulin signaling lifestyle factors limb amputation male mechanical properties migration mortality mouse model nanosystems non-healing wounds novel novel therapeutics phase 2 study porcine model pre-clinical preclinical efficacy pressure primary outcome product development protein aminoacid sequence public health relevance scaffold secondary outcome wound wound care wound closure wound healing

项目摘要

PROJECT SUMMARY/ABSTRACT Diabetes Mellitus (DM), a metabolic disorder characterized by defective insulin signaling and elevated blood glucose, has become a public health epidemic with half of the US population diagnosed with either DM or pre- diabetes. One of the most common and devastating sequelae of uncontrolled DM is the development of chronic non-healing wounds. An estimated 25% of diabetic patients develop chronic non-healing ulcers in their lifetime that, given the poor vascularity and immunodeficiency associated with diabetes, are highly susceptible to infection and frequently result in limb amputation. DM is currently the seventh leading cause of death in the U.S. Current management primarily focuses on controlling wound bioburden to promote wound healing, which includes pressure off-loading, antimicrobial medications and dressings, judicious wound care, and optimization of lifestyle factors. However, complete wound closure is complicated by impairment of cellular migration and function in DM wounds. Therefore, there is a pressing need to develop novel therapeutic methods for diabetic wounds that directly restore the molecular and cellular processes required to promote proper cutaneous repair. Injuries in diabetic patients often persist and progress. Chronic DM causes significant alterations to several physiologic wound healing mechanisms that impair timely cell infiltration/migration, granulation tissue formation, and wound contraction. Based on more than 20 years of research on wound healing management, we have developed a technologically innovative fibromodulin (FMOD)-based amino acid peptide sequence, SLI-F06, that markedly stimulates fibroblast and endothelial cell migration and myofibroblast differentiation/contraction to promote timely wound closure. Previously, we demonstrated that SLI-F06 significantly promotes acute wound healing without eliciting any adverse effects in preclinical animal studies at maximal feasible dosing as well as in ongoing Phase 1/2a clinical trial targeting acute wound healing. Excitingly, we have shown that repeated SLI- F06 administration significantly accelerates diabetic wound closure in a mouse model (NONcNZO10/LtJ) that closely simulates human type 2 DM. The goal of the current Fast-track SBIR application is to obtain the key preclinical efficacy and mechanism of action data for SLI-F06 as a repeatedly administered, locally applied therapeutic for diabetic wounds for expanding the clinical indication of SLI-F06. Overall, this proposal will accomplish key efficacy and mechanism of action (MOA) objectives to expedite commercialization of SLI-F06-based therapy for diabetic wounds. This product can significantly improve the quality of life of diabetic patients suffering from chronic wounds that can lead to amputations and death.

项目摘要/摘要糖尿病（DM），一种代谢性疾病，其特征是胰岛素信号和血液升高的特征葡萄糖已成为一种公共卫生流行病，其中一半的美国人口被诊断为DM或前糖尿病。不受控制的DM最常见和毁灭性的后遗症之一是慢性的发展非治疗伤口。估计有25％鉴于与糖尿病相关的血管性和免疫缺陷差，这非常容易受到感染并经常导致肢体截肢。 DM目前是美国第七大死亡原因当前管理主要专注于控制伤口生物负担以促进伤口愈合，这是包括卸载压力，抗菌药物和敷料，明智的伤口护理和优化生活方式因素。但是，由于细胞迁移的损害，完全伤口闭合是复杂的 DM伤口的功能。因此，需要开发新的糖尿病治疗方法直接恢复促进适当皮肤修复所需的分子和细胞过程的伤口。糖尿病患者的伤害经常持续和进展。慢性DM对几个生理伤口愈合机制损害了及时的细胞浸润/迁移，肉芽组织形成，和伤口收缩。根据有关伤口愈合管理的20多年的研究，我们已经开发了一种具有技术创新的纤维纤维蛋白（FMOD）的氨基酸肽序列SLI-F06，该氨基酸肽序列明显刺激成纤维细胞和内皮细胞迁移以及成肌纤维细胞的分化/收缩促进及时的伤口闭合。以前，我们证明SLI-F06显着促进了急性伤口在最大可行剂量和在正在进行的1/2A阶段中，针对急性伤口愈合的临床试验。令人兴奋的是，我们已经证明了重复的sli- F06给药可显着加速糖尿病伤口在小鼠模型（非cnzo10/ltj）中密切模拟人类2 dm。当前快速轨道SBIR应用程序的目的是获取密钥 SLI-F06的临床前疗效和动作数据的机理，作为反复给药，本地给药用于糖尿病伤口的治疗，以扩大SLI-F06的临床指示。总体而言，这提案将实现关键功效和行动机制（MOA）目标，以加快商业化基于SLI-F06的糖尿病伤口的治疗。该产品可以显着改善糖尿病的生活质量患有慢性伤口的患者会导致截肢和死亡。