HB-EGF regeneration to treat oral aphthous ulcers

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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.