Comprehensive assessment of the effectiveness of gene therapy in patients with chronic ischemia of the lower limbs

A.V. Shabunin¹, M.R. Kuznetsov^2,3, D.V. Matveev¹, E.E. Fedorov³, A.D. Matveev<sup>1

1</sup>Russian Medical Academy of Continuous Professional Education, Moscow
²Pirogov Russian National Research Medical University, Moscow
³Bauman City Clinical Hospital No. 29, Moscow

Aim: to evaluate the efficacy of conservative treatment of patients with chronic lower limb ischemia (CLLI) using genetically engineered therapy (Neovasculgen).
Patients and Methods: 49 patients with different degrees of arterial damage to the lower limbs participated in the study. Patients were divided into 2 groups: patients of the 1st group received standard conservative therapy, drug treatment of the 2nd group patients was supplemented with Neovasculgen, which was injected intramuscularly into the calf muscles of the affected limb by 1.2 mg at intervals of 14 days twice. The effectiveness of the treatment was assessed both on the basis of subjective (pain-free walking distance – PFWD) and objective (VEGF-A (vascular endothelial growth factor A) in peripheral blood, BNIP3 (BCL2/adenovirus E1B 19 kDa protein-interacting protein 3, proapoptosis protein of the B-cell lymphoma 2 family (BCL2) in the biopsy of the calf muscle affected limb) criteria.
Results: after 6 months, no significant dynamics, both positive and negative, were observed in 1st group patients for any of the indicators. Patients of the 2nd group had a significant increase in PFWD, an increase in VEGF-A in peripheral blood flowing directly from ischemic muscles, and a decrease in BNIP3 levels, especially in patients with intermittent claudication, corresponding to the II stage of ischemia according to the Fontaine-Pokrovsky classification.
Conclusion: the results of the study have shown that gene therapy should be recommended as part of a conservative treatment regimen for CLLI, primarily in patients with IIA and IIB ischemia. In addition, it is worth emphasizing the importance of using objective evaluation criteria (determination of the endothelial growth factor VEGF-A in peripheral blood, determination of the proapoptosis protein BNIP3 of the BCL2 family): it is the introduction of histochemical and biochemical criteria that can make the next step towards the creation of a «golden standard» of conservative treatment of CLLI.

Keywords: chronic ischemia of the lower limbs, morphological criteria, biochemical criteria, apoptosis, VEGF-A, BNIP3, gene therapy, therapeutic angiogenesis.
For citation: Shabunin A.V., Kuznetsov M.R., Matveev D.V. et al. Comprehensive assessment of the effectiveness of gene therapy in patients with chronic ischemia of the lower limbs. RMJ. 2019;2:21–25.