In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 132, No. suppl_3 ( 2015-11-10)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/circ.132.suppl_3.10200
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2015
detail.hit.zdb_id:
1466401-X
