Targeting the Nape-pld pathway for treatment of skin ulcers and improving diabetic wound healing

Author: Lia Dopp
Program: Medicine
Mentor(s): Sean Davies, PhD
Poster #: 4
Session/Time: A/2:40 p.m.

Abstract

Introduction:

Diabetes and associated complications cost $116 billion in 2007 with 33% of these costs linked to foot ulcers. Due to neuropathy and poor circulation, diabetes is a major risk factor for the development of skin ulcers resulting in 15-25% of diabetic patients having nonhealing skin wounds. We hypothesize that enhancing palmitoylethanolamide (PEA) levels, either through topical administration of PEA or of N-acyl phosphatidylethanolamine hydrolyzing phospholipase D (NAPE-PLD) activators to enhance PEA synthesis, will result in reduced skin injury and ulceration in response to ischemia and reperfusion (i.e. pressure ulcers) and more rapid healing of these skin wounds.

Methods:

We performed a pilot study to assess whether the pressure ulcer model could be used to test the role of NAPE-PLD in pressure ulcers. Four C57BL6 male mice, 28-31 grams, underwent three cycles of ischemia / reperfusion (I/R) by pinching a dorsal skinfold between two magnets for 6 h and then removing the magnets for 6 h. The injured (ulcerated) areas were treated topically with a sterile film of Vaseline or 2% PEA in Vaseline once daily.

Results:

The extent of I/R injury in this pilot study was less than we expected from the literature, with no wound reaching a score greater than 2. This may be because we are using C57BL6 mice rather than Balb/c mice often used with wound healing experiments. In future studies, we will increase the ischemia time to 18 hours while keeping the reperfusion time at 6 hours.

Conclusion:

The FDA has not approved a new wound-healing drug-based therapy in twenty years therefore this research proposes a new therapeutic strategy to target this major unmet need. If successful, this research would provide a novel, potential treatment for pressure ulcers using NAPE-PLD activators potentially minimizing the health risks that are associated with pressure ulcers.