HB-EGF regeneration to treat oral aphthous ulcers

HB-EGF再生治疗口腔阿弗他溃疡

• 批准号: 10081481
• 负责人: Benjamin Franklin McGraw
• 金额: $ 20.02万
• 依托单位: AURATION BIOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10081481
• 关键词: Address; Anesthesia procedures; Animal Model; Anti-Inflammatory Agents; Aphthous Stomatitis; Area; Beds; Binding; Biological; Biomedical Engineering; Biotechnology; Caucasians; Chronic; Clinical Trials; Collaborations; Combined Modality Therapy; Contracture; Cytoplasmic Granules; Data; Dehydration; Deposition; Development; Disease; Dose; Drug Kinetics; ERBB2 gene; ERBB3 gene; Ear; Encapsulated; Epidermal Growth Factor; Epidermal Growth Factor Receptor; Epithelial; ErbB4 gene; Family; Formulation; Funding; Gel; Goals; Growth Factor; Heparin Binding; Histologic; Human; Immunomodulators; In Vitro; Inflammatory; Intake; Lidocaine; Liquid substance; Local Anti-Infective Agents; Medical; Modeling; Mouthwash; Mus; Muscle; Natural regeneration; Operative Surgical Procedures; Oral; Oral cavity; Oral mucous membrane structure; Outcome; Pain; Patients; Pharmaceutical Preparations; Phase; Play; Population; Prevalence; Process; Property; Publishing; Quality of life; Radiation; Recurrence; Research Project Grants; Resolution; Rodent; Role; Safety; Scientist; Site; Surgical wound; System; Thick; Time; Tissues; Tongue; Topical application; Touch sensation; Translating; Translations; Trauma; Ulcer; United States National Institutes of Health; associated symptom; biodegradable polymer; commercialization; dietary; drug development; effective therapy; efficacy testing; epithelial wound; healing; heparin-binding EGF-like growth factor; improved; in vivo; in vivo Model; innovation; member; mouse model; neovascularization; novel; oral condition; oral mucositis; pain reduction; pre-clinical; prevent; release factor; skin ulcer; standard of care; success; symptom treatment; wound; wound closure; wound healing

Project Summary / Abstract We request NIH support to develop heparin-binding epidermal growth factor-like growth factor (HB-EGF) as treatments for oral aphthous ulcer disease: Chronic recurrent oral aphthous ulcers are the most common type of inflammatory condition of the oral mucosa with a prevalence of 2% to 10% in Caucasian populations. They can be a manifestation of trauma or a systemic inflammatory process or often they are truly idiopathic. They can cause severe pain and have the potential to limit oral intake of fluids. The standard of care currently is symptomatic treatment involving dietary changes and topical anti-inflammatories, antiseptics, or anesthesia. In severe cases, systemic immunomodulatory agents are used. Currently, there is no epithelization agent available that would address the histological problem. For this project, we will leverage the combined expertise of the Santa Maria Lab, which developed HB-EGF for topical administration in the oral cavity, with Auration Biotech, who have already successfully preclinically translated the same biologic to clinical trials for another indication. Our innovative approach aims to be the first available to accelerate aphthous ulcer wound healing that directly addresses the epithelium. We have shown that locally administered HB-EGF accelerates and thickens epithelialization and makes the neo epithelial layer more adherent to the underlying wound. Therefore, we hypothesize that this is likely to improve aphthous ulcer wound healing in a tongue surgical ulcer mouse model. Our aims are focused on optimizing our current treatment for this new indication and then confirming efficacy in a relevant in vivo model. Our Aims encompass: (1) optimizing the microgel delivery for tongue ulcers so that it can be applied to a more focused area of the oral cavity and (2) confirming the ability of the HB-EGF delivered by mucoadhesive microgels to improve tongue ulcer wound healing in our animal model. Our outcomes will be to show reduced epithelial separation and wound reopening, greater epithelial thickness, and earlier wound closure in HB-EGF treated tongue ulcers. If the outcomes of this Phase I project are reached, we will apply for Phase II funding to further commercial development. Ultimately, if successful, patients with aphthous ulcers achieve significantly reduced pain and avoid dehydration with the potential to significantly improve quality of life in these patients.

项目总结/摘要 我们请求NIH支持开发肝素结合表皮生长因子样生长因子（HB-EGF）， 口腔溃疡的治疗方法：慢性复发性口腔溃疡是最常见的类型 在高加索人群中，口腔粘膜炎症的患病率为2%至10%。他们 可能是创伤或全身炎症过程的表现，或者通常是真正的特发性。他们 可能导致剧烈疼痛，并有可能限制口服液体的摄入。目前的护理标准是 对症治疗，包括饮食改变和局部抗炎药、防腐剂或麻醉。在 严重病例，使用全身免疫调节剂。目前，没有上皮形成剂 可以解决组织学问题。在这个项目中，我们将利用 的圣玛利亚实验室，该实验室开发了HB-EGF用于口腔局部给药， 生物技术公司已经成功地将同一种生物制剂转化为另一种生物制剂的临床试验。 适应症 我们的创新方法旨在成为第一个可以直接加速阿弗他溃疡伤口愈合的方法， 针对上皮细胞。我们已经表明，局部施用HB-EGF加速和增厚， 上皮化，并使新上皮层更粘附于下面的伤口。所以我们 假设这可能改善舌外科溃疡小鼠模型中阿弗他溃疡伤口愈合。 我们的目标集中在优化我们目前对这种新适应症的治疗，然后确认在以下方面的疗效： 相关的体内模型。我们的目标包括：（1）优化微凝胶递送舌溃疡， 可以应用于口腔的更集中的区域和（2）证实HB-EGF递送的能力 通过粘膜粘附微凝胶改善我们动物模型中舌溃疡伤口的愈合。我们的成果将是 显示减少的上皮分离和伤口重新开放、更大的上皮厚度和更早的伤口 在HB-EGF治疗舌溃疡中的闭合。如果第一阶段项目取得成果，我们将申请 第二阶段资金用于进一步的商业开发。最终，如果成功的话， 显著减轻疼痛，避免脱水，有可能显著改善生活质量 在这些患者中。