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Scientific Publication in the Journal of Investigative Dermatology

May 20, 2020

We are happy to announce that on May 18, 2020, under the title “A dual-acting nitric oxide donor and phosphodiesterase 5 inhibitor promotes wound healing in normal and diabetic mice” (JID-2019-0913.R1) the Journal of Investigative Dermatology accepted a manuscript for publication as confirmed by their Principal Deputy Director Thomas Krieg, MD.

ABSTRACT – Chronic wounds affect a large percentage of the population world-wide and cause significant morbidity. Unfortunately, efficient compounds for the treatment of chronic wounds are as yet not available. Endothelial dysfunction, which is at least in part a result of compromised nitric oxide production and concomitant reduction in cGMP levels, is a major pathological feature of chronic wounds. Therefore, we designed and synthetized a compound with unique dual-acting activity (TOP-N53), acting as nitric oxide donor and phosphodiesterase 5 ihibitor, and applied it locally to full-thickness skin wounds in healthy and healing-impaired diabetic mice.

RESULTS – TOP-N53 promoted keratinocyte proliferation, angiogenesis and collagen maturation in healthy mice without accelerating the wound inflammatory response or scar formation. Most importantly, it partially rescued the healing impairment of genetically diabetic db/db mice by stimulating re-epithelialization and granulation tissue formation, including angiogenesis. In vitro studies with human and murine primary cells showed a positive effect of TOP-N53 on keratinocyte and fibroblast migration, keratinocyte proliferation, as well as endothelial cell migration and tube formation. These results demonstrate a remarkable healing-promoting activitiy of TOP-N53 by targeting the major resident cells in the wound tissue.

The responsible collaborating scientists partners from ETHZ responsible for this break-through study are the following: Maya Ben-Yehuda Greenwald, Carlotta Tacconi, Marko Jukic, Natasha Josi, Paul Hiebert, Jürgen Brinckmann, and Sabine Werner. From TOPADUR contributing scientists were Hermann Tenor and Reto Näf.