Pathohistological assessment of skeletal muscle after direct gene therapy with vegf165 of patients with peripheral arterial diseases

The aim was to elucidate impact of gene therapy with plasmid encoding vegf165 on the muscle tissue pathohistology of patients with peripheral arterial diseases. Twice repeated intramuscular injections of plasmid («Neovaskulgen», RN LP-000671 from 28.09.2011) were performed to 6 patients (ischemia grade IIb-III by Pokrovsky-Fontaine) according to specification. Standart tredmill test, ankle-brachial index estimation were performed. Histological study of injured muscle biopsies taken before and 3 months after injection was performed. In intact muscles therapy with vegf165 leads to increase of mean cross-sectional muscle fiber area without significant angiogenic effect. In muscles with decreased capillary density this therapy leads to blood supply improvement promoting regeneration of muscles by myosatellites proliferation and increase of mean cross-sectional muscle fiber area and connective tissue degradation. Treadmill test showed painless walking distance increased by 31,74% on average (from 94,96±49,79 m to 139,11±60,78 m, p<0,05) in all patients. There was correlation of pathohistological analysis with clinical data.