HB-EGF regeneration to treat oral aphthous ulcers

项目摘要/摘要 我们请求NIH支持开发肝素结合的表皮生长因子样生长因子(HB-EGF)作为 口腔溃疡的治疗：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 会导致剧烈疼痛，并有可能限制口服液体的摄入。目前的护理标准是 对症治疗包括改变饮食和局部使用消炎药、防腐剂或麻醉剂。在……里面 病情严重时，使用全身免疫调节剂。目前，还没有上皮剂。 这将解决组织学问题。对于这个项目，我们将利用综合的专业知识 圣玛丽亚实验室，该实验室开发了HB-EGF用于口腔局部给药，具有Auration 生物技术，他们已经成功地将相同的生物转化为另一种生物的临床前试验 指示。 我们的创新方法旨在成为第一个可以直接加速口腔溃疡伤口愈合的方法 处理上皮细胞。我们已经证明，局部应用HB-EGF可以加速和增厚 上皮化，并使新上皮层更贴附于底层伤口。因此，我们 假设这可能会改善舌部外科溃疡小鼠模型的口腔溃疡伤口愈合。 我们的目标是针对这一新的适应症优化我们目前的治疗方法，然后确认 一个相关的活体模型。我们的目标包括：(1)优化治疗舌溃疡的微凝胶输送，使其 可应用于口腔更集中的区域和(2)确认HB-EGF传递的能力 粘附性微凝胶促进舌溃疡创面愈合的实验研究我们的结果将是 显示上皮分离减少和伤口再开放，上皮厚度增加，伤口更早 HB-EGF治疗舌溃疡的闭合治疗。如果这一期项目取得成果，我们将申请 第二阶段为进一步的商业发展提供资金。最终，如果成功，口腔溃疡患者 显著减轻疼痛，避免脱水，并有可能显著提高生活质量 在这些病人身上。

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.