Abstract 10200: Translational Research of Novel Angiogenic Peptide for Wound Healing Drug; From Discovery to Clinical Trial
We developed a novel cationic peptide, AG30/5C, with angiogenic properties. Since it has both angiogenic and antimicrobial actions, it might be a candidate peptide for wound healing drug. We conducted a physician-initiated clinical trial of AG30/5C for severe skin ulcer in patients as an open label study. The primary outcome is safety because it is first in human trial on early stage. AG30/5C was administered with patients with skin ulcer twice per day for two weeks, and ulcer size and Methicillin-Resistant Staphylococcus Aureus amount was quantified as a secondary outcome. Two patients was registered until now and the skin ulcer of first patient was completely cured after AG30/5C treatment. The Methicillin-Resistant Staphylococcus Aureus amount of both patients was decreased during the AG30/5C treatment. This result suggests the potential of AG30/5C as a wound healing drug, however, improvement of stability and cost efficiency are required toward drug development. Thus, we addressed to the metabolites of AG30/5C which can provide a further optimized compound, SR-0379. SR-0379 also enhanced proliferation, tube formation, migration and contraction on human dermal fibroblast cells via the PI3K-Akt-mTOR pathway through integrin-mediated interactions. We evaluated the effect of SR-0379 on two different would healing model in rats, the full-thickness defects in diabetic condition and an acutely infected wound with the full-thickness defects and inoculation with S aureus. Treatment of SR-0379 significantly accelerated the wound healing compared to that of FGF2. The beneficial effects of SR-0379 on wound healing would be explained by enhanced angiogenesis, granulation tissue formation, proliferation and antimicrobial activity. These results clearly demonstrated that SR-0379 may have a potential for drug development in wound repairing, in especially critical colonization condition. Based on these results, we now conducted the physician-initiated clinical trial for severe skin ulcer in patients as a double blind study.
Author Disclosures: H. Nakagami: Other; Modest; Department of Health Development and Medicine was financially supported by Anges MG. R. Morishita: Ownership Interest; Modest; Ryuichi Morishita is a founder of AnGes MG, and a stockholder.. Other; Modest; Department of Clinical Gene Therapy was financially supported by Anges MG..
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