Expression of active matrix metalloproteinase-9 as a likely contributor to the clinical failure of aclerastide in treatment of diabetic foot ulcers

European Journal of Pharmacology
Trung T NguyenMayland Chang

Abstract

Chronic wounds are a complication of diabetes. Treatment for diabetic foot ulcers is complex with little clinical recourse, resulting in 108,000 lower-limb amputations annually in the United States alone. Matrix metalloproteinases (MMPs) play important roles in the pathology and in the repair of chronic wounds. We previously identified active MMP-8 and MMP-9 in wounds of diabetic mice and determined that MMP-8 accelerates wound repair, while MMP-9 is the culprit for the diabetic wound being refractory to healing. Aclerastide, a peptide analog of angiotensin II, recently failed in phase III clinical trials for treatment of diabetic foot ulcers. We demonstrate herein that treatment of wounds of diabetic mice with aclerastide results in elevated levels of reactive oxygen species and of active MMP-9, which is likely an important contributor to the failure of aclerastide in clinical trials.

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Citations

Sep 27, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Mengdie LiYijie Shi
Nov 19, 2019·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Trung T NguyenMayland Chang
May 28, 2019·Pharmaceuticals·Jeffrey I JonesMayland Chang
Jun 22, 2021·ACS Pharmacology & Translational Science·Charles Edwin Raja GabrielShahriar Mobashery
Oct 15, 2021·Reviews in Endocrine & Metabolic Disorders·Setareh SoltaniReza Yarani

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