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.

项目摘要 /摘要 我们要求NIH支持以开发肝素结合表皮生长因子样生长因子（HB-EGF）作为 口腔腹膜溃疡疾病的治疗：慢性复发性口腔溃疡是最常见的类型 口腔粘膜的炎症状况，高加索人群患病率为2％至10％。他们 可以是创伤或系统性炎症过程的表现，也可以是真正的特发性。他们 可能会引起严重的疼痛，并有可能限制流体的口服摄入量。目前的护理标准是 涉及饮食变化和局部抗炎，防腐剂或麻醉的有症状治疗。在 严重的病例，使用全身免疫调节剂。目前，没有上皮化代理 可以解决组织学问题。对于这个项目，我们将利用合并的专业知识 Santa Maria Lab开发了用于口腔局部给药的HB-EGF，并带有auration Biotech，他们已经成功地将同样的生物学转化为另一个生物学试验 指示。 我们的创新方法旨在首次使用直接加速溃疡伤口愈合的方法 解决上皮。我们已经表明，本地管理的HB-EGF加速并增厚 上皮化，并使新上皮层更加遵守潜在的伤口。因此，我们 假设这可能会改善舌外科手术溃疡小鼠模型中的孔隙溃疡伤口愈合。 我们的目标是针对我们当前的新迹象进行优化，然后确认有效性 相关的体内模型。我们的目标包括：（1）优化舌溃疡的微凝胶输送，以便 可以应用于口腔的更集中区域，（2）确认已交付的HB-EGF的能力 通过粘粘性微凝胶来改善我们动物模型中的舌溃疡伤口愈合。我们的结果将是 显示上皮分离减少和重新开放，上皮厚度更大，较早的伤口 HB-EGF治疗的舌溃疡中的闭合。如果达到I阶段项目的结果，我们将申请 第二阶段的资金用于进一步的商业发展。最终，如果成功的话，患有腹腔溃疡的患者 显着减轻疼痛并避免脱水，并有可能显着改善生活质量 在这些患者中。