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One Possible Answer to Healing Chronic Diabetic Foot Ulcers

Polydeoxyribonucleotide (PDRN), an adenosine A2A receptor agonist, improves wound healing…. 

The exact mechanism by which diabetes impairs wound healing is not fully understood, but may include abnormal inflammatory cell response, impaired neovascularization, decreased synthesis of collagen and increased levels of proteinases. As a result of all of the unknowns, management of diabetic foot ulcers still represents a challenge in the medical community.

Polydeoxyribonucleotide (PDRN) is a preparation used in therapy as a tissue repair stimulating agent in diseases characterized by a loss of substance such as chronic wounds and burns. It consists of low molecular weight deoxyribonucleic acid (DNA) fractions that are combined by phosphodiester bonds. The compound is extracted from the sperm of trout bred for human food purposes and is then purified. In vitro PDRN has been shown to enhance the growth rate of human fibroblasts and osteoblasts in cultures. PDRN also was shown to enhance wound healing in several experimental models.

A prospective randomized, double blind, placebo controlled clinical trial was conducted in Italy to evaluate how effective PDRN was treatment of patients who suffered from chronic diabetic foot ulcers. Patients were all Caucasian, with type 1 or 2 diabetes and were metabolically stable established by two prior A1C levels. The all suffered from chronic, hard to heal foot ulcers which were free of visible infection or necrotic debris, ulcer size between 1.0 and 16.0 cm2, present for at least 4 weeks and an ulcer grade 1 or 2 according to Wagner grade scale.

Patients were randomly assigned to receive placebo (n=106) or PDRN (n=110). Baseline comparisons were similar among the two groups. Treatment was administered daily intramuscularly for 5 days a well and by perilesional route 2 days a week, all for 8 weeks. The primary endpoint was the occurrence of complete healing of the ulcer within the 8 week treatment period. Complete healing was defined as epithelialization of the wound in the absence of drainage that lasted until the end of the follow-up period which was an additional 4 weeks. The secondary endpoints were the mean time, expressed in days, required to complete wound closure within the end of treatment and the change in the epithelized area of the ulcer at the end of the treatment. All randomized patients were including in analysis based on an intention to treat approach.

After 8 weeks, ulcers closed in 37.3% of the PDRN group compared with 18.9% of the placebo group. Only taking those who completed the study, complete healing occurred in 40.6% of the PDRN group compared with 22.0% of the placebo group after 8 weeks. No recurrence was observed in those patients who experienced complete healing. The median time to complete wound closure was 49 days for placebo and 30 days for the PDRN group. The median percentage of reepithelialized wound surface was 82.2% for the PDRN treatment group, compared with 49.3% of the placebo group. Moreover, only 2 patients of the 110 in the PDRN group reported a worsening of the wound, compared to 20 of 106 patients in the control group.

Safety of the treatment was found to be excellent with just the occasional headache and flu-like symptoms being reported. Injection site itching was also reported in the PDRN group in 18 of the patients.

The results of the study indicate that PDRN could be successfully used to facilitate healing in patients with chronic diabetic foot ulcers.

Practice Pearls:
  • Polydeoxyribonucleotide (PDRN) is a preparation used in therapy as a tissue repair stimulating agent in diseases characterized by a loss of substance such as chronic wounds and burns.
  • The results of the study indicate that PDRN could be successfully used to facilitate healing in patients with chronic diabetic foot ulcers.

Squadrito, Francesco, Bitto, Alessandra, Altavilla, Domenica, et al. The Effect of PDRN, an Adenosine Receptor A2A Agonist, on the Healing of Chronic Diabetic Foot Ulcers: Results of a Clinical Trial. The Journal of Clinical Endocrinology and Metabolism. 2014: 99(5). Accessed on June 19, 2014 from http://press.endocrine.org.cuhsl.creighton.edu/doi/abs/10.1210/jc.2013-3569