A novel anti-scar peptide for cutaneous wound repair

一种用于皮肤伤口修复的新型抗疤痕肽

• 批准号: 8455289
• 负责人: Shen Pang
• 金额: $ 19.97万
• 依托单位: SCARLESS LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8455289
• 关键词: Adult; Adverse effects; Affect; Algorithms; Alternative Therapies; Amino Acids; Animals; Appearance; Area; Atrophic condition of skin; Biological Models; Biomechanics; Burn injury; Bypass; Cells; Cicatrix; Clinical; Cornea; Cosmetics; Cutaneous; Data; Dental Hygiene; Development; Disease; Dose; Drug Formulations; Extracellular Matrix; FDA approved; Face; Family suidae; Fibrosis; Goals; Granuloma; Growth; Histology; Human; Impairment; Intention; Intravenous; Investigational Drugs; Keloid; Keratopathy; Kidney; Knockout Mice; Laboratories; Lasers; Liver; Liver Cirrhosis; Lung; Microstomia; Modeling; Mus; Ointments; Operative Surgical Procedures; Oral; Outcome Measure; Pathologic; Patients; Peptides; Pharmaceutical Preparations; Phase; Pilot Projects; Placebos; Prevention; Prevention strategy; Process; Production; Proteins; Pulmonary Fibrosis; Radiation; Rattus; Recurrence; Refractory; Research; Safety; Scleroderma; Side; Silicones; Skin; Small Business Innovation Research Grant; Steroids; Techniques; Tensile Strength; Testing; Time; Toxicology; Trauma; Treatment Protocols; Visual; Wound Healing; analog; base; body system; cleft lip and palate; commercialization; cost; design; fetal; fibromodulin; improved; innovation; novel; operation; palate repair; primary outcome; protein aminoacid sequence; public health relevance; repaired; safety study; standard of care; success; technological innovation; wound

DESCRIPTION (provided by applicant): Cutaneous fibrosis (scarring) affects up to 100 million patients per year as a result of 55 million elective operations and 25 million operations after trauma. Besides concerns of cosmesis, scarring can have significant functional sequel. Overall, scar prevention strategies for skin are minimally effective. Currently available techniques focus on reducing the appearance of already formed scars (e.g., silicone sheeting, topical ointments, and lasers). Other scar reduction strategies that target the scar formation process such as steroids and radiation can have undesirable side effects. With these substantial limitations, there remains a pressing need for the development of alternative therapies for the prevention of cutaneous scarring. Through a sustained, 11-year research effort examining models of fetal wound healing; we have identified fibromodulin (FMOD) as a novel molecule required for fetal scarless skin repair. FMOD protein decreases scarring and improves extracellular matrix (ECM) organization in adult wounds. These finding have been confirmed across multiple mammalian species. In a technological innovation, we have identified a 40 amino acid peptide sequence, F06-C40, with similar anti-fibrotic effects to the full FMOD protein. This allows us to bypass costly cell-based techniques for protein production in favor of a synthetic FMOD peptide that can be produced rapidly, inexpensively, and with high purity. Most recently, using a pig model we demonstrated in pilot studies that both FMOD protein and its peptide derivative, F06-C40, significantly reduce scar formation. In this proposal we will test the hypothesis that F06-C40 will have improved efficacy without a change in safety in comparison to placebo for the reduction of cutaneous scar formation. AIM 1 (Months 1-12): Optimize F06-C40 for cutaneous scar prevention. AIM 1 will optimize the dose and duration of F06-C40 for cutaneous scar reduction. A porcine primary intention wound closure model will be used. Porcine skin is the closest animal equivalent to human skin, and is the FDA-preferred model system for testing of wound healing products. Primary outcome measures will include improved gross visual appearance without reduction in wound tensile strength. AIM 2 (Months 13-24): Perform F06-C40 systemic and local toxicology studies. AIM 2 will initiate F06- C40 safety studies required by the FDA for an Investigational New Drug (IND) submission. An escalating dose intravenous study will be performed in rats, and an escalating dose intradermal study will be conducted in pigs. Cutaneous scars cause significant functional and cosmetic impairment. To this day, there exist no FDA approved drugs for prevention of scar recurrence. This Phase I SBIR proposal focuses on optimizing the treatment regimen for F06-C40 and proving its safety and efficacy.

描述（由申请人提供）：皮肤纤维化（疤痕）每年由于5500万个选修手术和创伤后的2500万手术而影响多达1亿例患者。除了担心cosmess，疤痕还具有明显的功能续集。总体而言，皮肤的疤痕预防策略至少有效。目前可用的技术着重于减少已经形成的疤痕的外观（例如，硅胶板，局部药膏和激光器）。针对疤痕形成过程（例如类固醇和辐射）的其他减少疤痕策略可能会产生不良的副作用。有了这些重大局限性，仍需要迫切需要开发预防皮肤疤痕的替代疗法。通过持续的11年研究工作，研究了胎儿伤口愈合的模型；我们已经将纤维瘤蛋白（FMOD）鉴定为胎儿无疤皮修复所需的新分子。 FMOD蛋白会减少成年伤口中的疤痕并改善细胞外基质（ECM）组织。这些发现已在多种哺乳动物物种中得到证实。在技​​术创新中，我们已经确定了40个氨基酸肽序列F06-C40，与全FMOD蛋白具有相似的抗纤维化作用。这使我们能够绕过蛋白质生产的昂贵的基于昂贵的细胞技术，而有利于合成的FMOD肽，该肽可以迅速，廉价且具有较高的纯度生产。最近，我们使用猪模型在试点研究中证明了FMOD蛋白及其肽衍生物F06-C40均显着降低疤痕的形成。在此提案中，我们将测试F06-C40的假设 与安慰剂减少皮肤疤痕形成相比，没有安全性的变化而没有改变安全性。 AIM 1（1-12个月）：优化F06-C40，以预防皮肤疤痕。 AIM 1将优化F06-C40的剂量和持续时间，以减少皮肤疤痕。将使用猪一级意图伤口闭合模型。猪皮肤是与人皮肤的最接近的动物，并且是用于测试伤口愈合产物的FDA偏爱模型系统。主要的结局指标将包括改善视觉外观，而不会降低伤口拉伸强度。目标2（13-24个月）：执行F06-C40系统和局部毒理学研究。 AIM 2将启动FDA要求提交的FDA要求的F06-C40安全研究。将在大鼠中进行一项不断升级的剂量静脉内研究，并将在猪中进行一项不断升级的剂量皮内研究。皮肤疤痕会导致严重的功能和化妆品障碍。直到今天，还没有FDA批准的药物可预防疤痕复发。该阶段I SBIR提案着重于优化F06-C40的治疗方案，并证明其安全性和功效。