Peripheral arterial occlusive disease (PAOD) of lower extremities is becoming more prevalent worldwide. The general prognosis is particularly negative with a high prevalence of
coronary heart disease and
cerebrovascular disease.
Diabetic foot ulcers occur in 15% of all the patients with diabetes and proceed to lower-leg
amputations. In diabetic
ulcers, wound healing is impaired because of delayed angiogenesis. In both pathological conditions, therapeutic angiogenesis using angiogenic
growth factors, particularly
Vascular Endothelial Growth Factor VEGF, is expected to be a valuable treatment. The most used approaches are based on
VEGF local delivery or gene therapy, but they failed to meet the expected primary goals of
therapy.
Adenosine receptor stimulation can induce
VEGF expression in many types of cells and this may be achieved by stimulating the A(2A) or A(2B) receptor or both, following the signalling pathways activated by
hypoxia. Polideoxyribonucleotide (PDRN) is obtained from sperm trout by an extraction process. The compounds hold a mixture of
deoxyribonucleotides polymers with chain lengths ranging between 50 and 2000 bp. PDRN is able to stimulate
VEGF production during pathological conditions of low tissue perfusion. It likely acts through the stimulation of A(2A) receptors. Furthermore, acute and chronic toxicity studies showed a good safety profile. PDRN has been shown to be effective in an experimental model of PAOD, hind limb
ischemia, impaired wound healing and
burn injury. Preliminary studies and ongoing clinical trials predict a significant therapeutic efficacy in patients. These data lead to hypothesize a role for PDRN in therapeutic angiogenesis.