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.

World’s First Clinical Case of Gene-Activated Bone Substitute Application

“…Therefore, we used the plasmid DNA encoding vegf gene to make the gene-activated bone substitute. Reparative osteogenesis, as a clinical efficacy indicator, could be achieved both due to an obvious angiogenic effect of the gene construct [18–20] and owing to the direct VEGF effect on bone tissue cells.…”

“…The first one is the composite scaffold of bovine collagen and synthetic hydroxyapatite (granules with diameter of 500–1000  μ m) registered as a bone substitute (CJSC Polystom, Russia) and approved for clinical use in Russia, the second one is a supercoiled naked plasmid DNA with cytomegalovirus promoter and gene encoding VEGF which is the active substance of “Neovasculgen” [18]. We made the gene-activated bone substitute in the form of rectangular sponge-like matrix (size of 20 × 10 × 10 mm, weight of 200 ± 10 mg) containing 0.2 mg of the gene constructs.…”

“…This gene construct is an active substance of the drug “Neovasculgen” (PJSC Human Stem Cells Institute, Russia) which has been shown to be safe and highly effective in the treatment of patients with chronic lower limb ischemia (CLI) of stages 2a-3 and is approved for a clinical use in the territories of Russia and Ukraine [18]. …”

Assessment of Genetic Mutations DMD, DYSF, EMD, LMNA, DUX4, DMPK, ZNF9, PABPN1 Genes Induction Duchenne Muscular Dystrophy

“…The resulting mixture for 24 hours at -20°C was incubated. [21][22][23][24][25][26][27] 2. Then for 45min at 4°C and was centrifuged at 12000 rpm era.…”

Current status of ex vivo gene therapy for hematological disorders: a review of clinical trials in Japan around the world

“…Accumulating clinical evidence has demonstrated the safety and benefits of several types of gene therapy. Currently, 78.1 % of 2210 protocols are at phase I or I/II (http://www.wiley.com/legacy/wileychi/genmed/ clinical/), but six gene therapy drugs have been approved in a limited number of countries [3][4][5][6][7].…”