Protein therapeutic to facilitate healing of chronic wounds.

促进慢性伤口愈合的蛋白质治疗剂。

基本信息

批准号：
9896846
负责人：
Tao Tan
金额：
$ 94.85万
依托单位：
TRIM-EDICINE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2021-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9896846
关键词：
Ablation Affect Animal Model Area Biological Biomedical Research Biotechnology Blood Circulation Canis familiaris Cell membrane Cell physiology Cellular Structures Chemistry Chronic Cicatrix Clinical Protocols Clinical Research Clinical Trials Collaborations Contracts Cream Critical Care Cyclic GMP Data Development Diabetes Mellitus Disease Dose Drug Controls Drug Kinetics Ensure Evaluation Family suidae Formulation Functional disorder Genes Goals Health Care Costs Heart Human Incidence Intravenous Investigational Drugs Investigational New Drug Application Laboratories Lead Longevity Medical center Modeling Mus Muscle National Institute of General Medical Sciences Natural regeneration No-Observed-Adverse-Effect Level Obesity Ohio Organ Pathology Patients Pharmaceutical Preparations Pharmacodynamics Phase Physiological Physiology Placebos Process Production Protein Family Proteins Protocols documentation Public Health Quality Control Rattus Recombinants Research Research Contracts Rivers Rodent Role Safety Skin Skin injury Small Business Innovation Research Grant TRIM Family TRIM Gene Testing Therapeutic Therapeutic Agents Tissue membrane Tissues Topical agent Topical application Toxicology Transgenic Mice Trauma United States United States Food and Drug Administration Universities aging population analytical method chronic ulcer chronic wound commercialization effective therapy gene repair healing human subject injury and repair intravenous administration irritation meetings non-healing wounds novel operation phase 1 study preclinical study programs prototype repaired research and development scale up skin irritation skin wound therapeutic protein tissue injury tissue regeneration tissue repair wound care wound healing

项目摘要

Project Summary This proposal builds upon the advances from the SBIR-Phase I program (R43GM123887), targeting the development of recombinant human MG53 (rhMG53), a novel tissue repair protein, as a topical therapeutic agent to facilitate healing of chronic wounds. Wound care represents a challenging problem to the public health, as no effective treatments for chronic non-healing wounds are available. MG53 is an essential component of cell membrane repair that protects against tissue injuries. Research and development efforts at TRIM-edicine, Inc. have established that rhMG53 protein has great potential in facilitation of wound healing and reduction of scar formation. From the SBIR-Phase I program we obtained proof-of-concept data that support our translational and commercialization effort toward developing rhMG53 as a protein therapeutic to treat chronic wounds. We developed the protocol for scale-up production of rhMG53 and the analytical methods for quantification and quality control of rhMG53. We obtained promising data to support the efficacy for rhMG53 in treatment of cutaneous wounds in multiple animal models. We also conducted non-GLP toxicological studies in rodent and dog models and found that rhMG53 as a topical cream did not cause irritation to the skin. No-observed-adverse-effect-level with intravenous administration is >40 mg/kg in rats, supporting the safety of rhMG53 to treat chronic wounds. In this SBIR-Phase II application, we outlined a milestone-driven research plan with deliverable matrixes to reach the goal of filling an Investigational New Drug (IND) application with the FDA to initiate the human clinical trials. Our understanding of MG53’s biological role in tissue repair-regeneration support the multi-cellular function of MG53 in promoting the healing process, as well as in mitigation of scarring associated with dermal injuries. We envision that rhMG53 has advantage over the current paradigms to treat human chronic wounds.

项目概要该提案以 SBIR-第一阶段计划 (R43GM123887) 的进展为基础，针对开发重组人 MG53 (rhMG53)，一种新型组织修复蛋白，作为局部治疗剂促进慢性伤口愈合的试剂对公众来说是一个具有挑战性的问题。 MG53 是治疗慢性不愈合伤口的有效方法。细胞膜修复的组成部分，可防止组织损伤。 TRIM-edicine, Inc. 已确定 rhMG53 蛋白在促进伤口愈合方面具有巨大潜力从 SBIR-第一阶段项目中，我们获得了概念验证数据：支持我们开发 rhMG53 作为治疗蛋白的转化和商业化努力我们开发了 rhMG53 的放大生产方案和分析方法。 rhMG53 的定量和质量控制方法我们获得了有希望的数据来支持其功效。我们还针对 rhMG53 在多种动物模型中治疗皮肤伤口进行了非 GLP 试验。对啮齿动物和狗模型进行的毒理学研究发现，rhMG53 作为外用乳膏不会引起大鼠静脉内给药时未观察到的皮肤刺激水平>40 mg/kg，支持 rhMG53 治疗慢性伤口的安全性在这个 SBIR-II 期应用中，我们概述了一个。具有可交付矩阵的里程碑驱动的研究计划，以达到填充研究性新药的目标 (IND) 向 FDA 申请启动人体临床试验我们对 MG53 生物学作用的了解。在组织修复再生中支持 MG53 促进愈合过程的多细胞功能，如我们认为 rhMG53 在减轻与皮肤损伤相关的疤痕方面具有优势。当前治疗人类慢性伤口的范例。