The first experience of gene therapy for the complex treatment of no-option chronic limb-threatening ischemia

Aim. To evaluate the effects of complex treatments with no-option chronic limb-threatening ischemia patients with ulcers, using plasmid-based vascular endothelial growth factor-165 (VEGF-165) gene therapy in a one year follow-up period. Methods. In total, 43 patients with no-option chronic limb-threatening ischemia were enrolled in a one year follow-up study. All patients received standard conservative treatment in combination with gene therapy. The mean patient age was 68.0 ± 9.8 years; 65 % men and 35 % women. Patients were divided into four subgroups according to WIfI (Wound, Ischemia, and foot Infection) combinations: 130 - 37 % (n = 16); 131 - 21 % (n = 9); 230 - 21 % (n = 9), and 231 - 21 % (n = 9). Effectiveness criteria were set at major amputation rates, amputation-free survival rates, total mortality, and rates of ulcer healing in the one year follow-up period. Results. Major amputation rates, amputation-free survival rates, total mortality, and rates of ulcer healing during the one year follow-up were; 28, 63, 12 and 51 %, respectively. Separately, a subgroup of WIfI 130 combination patients experienced significant improvements (p = 0.01): amputation-free survival - 94 %, limb salvage rates - 100 %, and rate of ulcer healing - 88 %. Conclusion. Using a plasmid-based VEGF-165 gene therapy approach in the subgroup with the WIfI 130 combination was beneficial. Gene therapy was not effective in patients with large ulcer areas and depth, and local infections (subgroups; 230 and 231). The higher WIfI combinations led to an increase in major amputation rates, reduced amputation-free survival and ulcer healing rates. Total mortality was independently not associated with ulcer area and depth, and severity of local infection. Total mortality between subgroups 130, 131, 230, 231 for WIfI combinations during 1 year of follow-up was not statistically differences (log-rank test, p = 0.67)