Results of Treating Patients with Critical Limb Ischemia Using a Naked Plasmid-based Vascular Endothelial Growth Factor 165 (pl-VEGF165) Gene Therapy

Chervyakov V. Yuriy, Staroverov N. Ilya, Nam H. Ha

Yaroslavl State Medical University of the Public Health Ministry of the Russian Federation, Yaroslavl, Russia. , Yaroslavl, Russia

Date, time and location: 2018.05.26 13:30, Exhibition area, 1st Floor. Zone – B

Abstract

Aims:To evaluate the effectiveness of apl- VEGF165 gene therapy (Neovasculgen) in patients with stage III chronic lower limb ischemia (CLI) according to Fontaine classification within the period of 3 to 5 years.

Materials and method: A total of 52 patients (n=52) with CLI were enrolled with a mean age of 65.0 ± 11.38 years from 2009 to 2017. After DDUS examination and DSA, all patients were non-candidates for surgical or endovascular revascularization. Patients received standard conservative therapy(SCT), a course of Prostaglandin E1 and incombination with double injection of apl-VEGF165 gene drug (1.2 mg) into the ischemic limb muscles.

Efficacy endpoints: the limb salvage rate, the survival rate, the pain-free walking distance (PFWD), blood flow linear velocity (BFLV), ankle-brachial index (ABI).These examinations were carried out initially, after and yearly. Surgical revascularization hasnot been carried out.

Results:The limb salvage rate was 86%, the survival rate was 88%. Baseline PFWD was 24± 12m. After 1 year, the mean value PFWD was 279 ±126m(p = 0.006) by the end of the study. After 5 years of follow-up, ABI increased from 0.27 ± 0.1 to 0.33 ± 0.14 (p = 0.05) and BFLV increased from 10.0 ± 6.9cm/s to 14.2 ± 9.8cm/s (p = 0.01).The result of treatment: in 69% of cases (n=36) was a significant improvement; in6% of cases(n=3) was a satisfactory result (PFWD increased to 100m); in 25% of cases (n=13) was unsatisfactory results: progression of CLI followed- necrosis formed on the foot, 7 patients underwent high amputation, 6 patients died (2 after amputation).

Conclusion:The use of pl-VEGF165 in combination with SCT in patients with CLI demonstrated a significant improvement in PFWD (p=0.006),in ABI (P=0.05),in BFLV (p=0.01). In 69% of cases was a significant improvement clinical signs.