NorLeu³-Angiotensin (1-7) [DSC127] as a Therapy for the Healing of Diabetic Foot Ulcers

Abstract

Diabetes is a disorder that is well known to delay wound repair resulting in the formation of colonized chronic wounds. Over their lifetime, diabetic patients have a 25% incidence of foot ulcers (DFUs), which contribute to increased risk of morbidity, including osteomyelitis and amputations, and increased burden to the healthcare system. The only active product approved for the treatment of diabetic ulcers, Regranex, is not widely used due to minimal proven efficacy and recent warnings added to the Instructions for Use. A novel topical agent that accelerates healing and increases the proportion of fully healed DFUs, DSC127 [aclerastide; active ingredient, NorLeu-angiotensin (1-7) (NorLeu-A(1-7))], is recruiting patients in Phase III clinical trials (NCT01830348 and NCT01849965). NorLeu-A(1-7) is an analog of the naturally occurring peptide, angiotensin 1-7. The mechanisms of action include induction of progenitor proliferation, accelerated vascularization, collagen deposition, and re-epithelialization. Current modalities for the treatment of DFUs include strict offloading, bandaging, debridement and, on a limited basis, application of Regranex. Novel potent therapies are needed to combat this significant burden to the diabetic patient and the healthcare system. Preclinical and clinical research shows that DSC127 is highly effective in the closure of diabetic wounds and is superior to Regranex in animal studies. Clinical development of DSC127 as a topical agent for the healing of DFU is underway. Further investigation into the mechanisms by which this product accelerates healing is warranted.

Inflammation in Chronic Wounds

“…Clinically, however, becaplermin has demonstrated only modest improvements in healing diabetic and pressure ulcers, but it and other growth factors have been used off-label in various acute and chronic wounds to some degree of success [70]. Recently, an angiotensin receptor agonist called aclerastide—also for the treatment of diabetic foot ulcers—advanced to phase III clinical trials, where, unfortunately, the study was terminated after conducting futility determinations [73]. Other growth factors, such as bFGF and VEGF, have similarly shown mixed clinical results despite promising in vitro and animal studies [74,75,76,77,78,79,80].…”

Angiotensin-(1–7) and Vascular Function

“…Of the Ang-(1-7) analogues, DSC127 is currently in a phase III clinical trial testing the safety and efficacy of topical application in accelerating the healing of diabetic foot ulcers (13).…”

Targeting the Protective Arm of the Renin-Angiotensin System to Reduce Systemic Lupus Erythematosus Related Pathologies in MRL-lpr Mice

“…Results from our study show definite benefit in several SLE pathologies that are likely due to reducing oxidative damage, immune activation and BM dysfunction. Both A(1-7) and NorLeu have shown safety and efficacy in other diseases ( 67 – 69 ). Our results show that there is likely a protection of the tissue in this SLE model which in turn likely leads to lower antigen burden available to activate immune cells.…”