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.

项目概要/摘要糖尿病 (DM) 是一种代谢性疾病，其特征是胰岛素信号传导缺陷和血糖升高葡萄糖已成为一种公共卫生流行病，一半的美国人口被诊断患有糖尿病或糖尿病前期糖尿病。不受控制的糖尿病最常见和最具破坏性的后遗症之一是发展为慢性糖尿病不愈合的伤口。据估计，25% 的糖尿病患者一生中会出现慢性不愈合溃疡鉴于与糖尿病相关的血管供应不良和免疫缺陷，很容易受到感染并经常导致截肢。糖尿病目前是美国第七大死因。目前的治疗主要集中在控制伤口生物负载以促进伤口愈合，这包括减压、抗菌药物和敷料、明智的伤口护理和优化生活方式因素。然而，由于细胞迁移和细胞迁移受损，伤口的完全闭合变得复杂。在 DM 伤口中发挥作用。因此，迫切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。糖尿病患者的损伤常常持续存在并不断进展。慢性糖尿病会导致一些方面的显着改变生理性伤口愈合机制会损害及时的细胞浸润/迁移、肉芽组织形成，和伤口收缩。基于 20 多年的伤口愈合管理研究，我们开发了一种技术创新的基于纤维调节蛋白 (FMOD) 的氨基酸肽序列 SLI-F06，显着刺激成纤维细胞和内皮细胞迁移以及肌成纤维细胞分化/收缩促进伤口及时闭合。之前，我们证明 SLI-F06 显着促进急性伤口在临床前动物研究中，在最大可行剂量以及正在进行针对急性伤口愈合的 1/2a 期临床试验。令人兴奋的是，我们已经证明重复的 SLI- 在小鼠模型 (NONcNZO10/LtJ) 中，F06 给药显着加速糖尿病伤口闭合，非常接近人类 2 型糖尿病。当前Fast-track SBIR应用的目标是获取密钥 SLI-F06 作为重复给药、局部治疗的临床前疗效和作用机制数据应用于糖尿病伤口治疗，扩大SLI-F06的临床适应症。总体而言，这该提案将实现关键功效和行动机制（MOA）目标，以加速商业化基于 SLI-F06 的糖尿病伤口治疗方法。该产品可显着改善糖尿病患者的生活质量患有可能导致截肢和死亡的慢性伤口的患者。