title: pCMV-vegf165 Intramuscular Gene Transfer is an Effective Method of Treatment for Patients With Chronic Lower Limb Ischemia.
abstract: Effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. There are a number of choices available to the vascular surgeon. Open or endovascular revascularization is the treatment of choice when applicable. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression. Therefore, new methods of treatment are needed. We conducted a phase 2b/3 multicenter randomized controlled clinical trial of the intramuscular transfer of a plasmid DNA encoding vascular endothelial growth factor (VEGF) 165 with cytomegalovirus promotor (CMV) in patients with atherosclerotic lower limb ischemia. A total of 100 patients were enrolled in the study, that is, 75 patients were randomized into the test group and received 2 intramuscular injections of 1.2 mg of pCMV-vegf165, 14 days apart together with standard pharmacological treatment. In all, 25 patients were randomized into the control group and received standard treatment only. The following end points were evaluated within the first 6 months of the study and during a 1.5-year additional follow-up period: pain-free walking distance (PWD), ankle-brachial index (ABI), and blood flow velocity (BFV). The pCMV-vegf165 therapy appeared to be significantly more effective than standard treatment. The PWD increased in the test group by 110.4%, 167.2%, and 190.8% at 6 months, 1 year, and 2 years after treatment, respectively. The pCMV-vegf165 intramuscular transfer caused a statistically significant increase in ABI and BFV. There were no positive results in the control group. Thus, pCMV-vegf165 intramuscular gene transfer is an effective method of treatment of moderate to severe claudication due to chronic lower limb ischemia.
authors.affiliation: OJSC "Human Stem Cells Institute", Moscow, Russia Department of Morphology and General Pathology, Kazan (Volga region) Federal University, Kazan, Russia.
authors.forename: Roman V
authors.initials: RV
authors.lastname: Deev
authors.affiliation: OJSC "Human Stem Cells Institute", Moscow, Russia Department of Maxillofacial Surgery, A.I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia Department of Maxillofacial Surgery, A.I. Burnazyan Medical Biophysical Center, Moscow, Russia bozo.ilya@gmail.com.
authors.forename: Ilia Y
authors.initials: IY
authors.lastname: Bozo
authors.affiliation: Department of Angiology and Vascular Surgery, Ryazan State I.P. Pavlov Medical University, Ryazan, Russia.
authors.forename: Nina D
authors.initials: ND
authors.lastname: Mzhavanadze
authors.affiliation: Department of Vascular Surgery, Russian National Research Center of Surgery, Moscow, Russia.
authors.forename: Dmitriy A
authors.initials: DA
authors.lastname: Voronov
authors.affiliation: Department of Vascular Surgery, Russian National Research Center of Surgery, Moscow, Russia.
authors.forename: Aleksandr V
authors.initials: AV
authors.lastname: Gavrilenko
authors.affiliation: Department of Surgery, Yaroslavl State Medical Academy, Yaroslavl, Russia.
authors.forename: Yuriy V
authors.initials: YV
authors.lastname: Chervyakov
authors.affiliation: Department of Surgery, Yaroslavl State Medical Academy, Yaroslavl, Russia.
authors.forename: Ilia N
authors.initials: IN
authors.lastname: Staroverov
authors.affiliation: Department of Angiology and Vascular Surgery, Ryazan State I.P. Pavlov Medical University, Ryazan, Russia.
authors.forename: Roman E
authors.initials: RE
authors.lastname: Kalinin
authors.affiliation: Department of Angiology and Vascular Surgery, Ryazan State I.P. Pavlov Medical University, Ryazan, Russia Deceased.
authors.forename: Pavel G
authors.initials: PG
authors.lastname: Shvalb
authors.affiliation: OJSC "Human Stem Cells Institute", Moscow, Russia.
authors.forename: Artur A
authors.initials: AA
authors.lastname: Isaev
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000628:therapy*; D017023:Coronary Angiography; D003587:Cytomegalovirus; D016228:Endothelial Growth Factors; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007273:Injections, Intramuscular; D007511:Ischemia / Q000628:therapy*; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012426:Russia; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*; D016138:Walking
chemical_list: D016228:Endothelial Growth Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: VEGF165; chronic lower limb ischemia; clinical trial; gene therapy