Optimization of adenovirus-mediated endothelial nitric oxide synthase delivery in rat hindlimb ischemia (original) (raw)
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Gene therapy of the ischemic lower limb — Therapeutic angiogenesis
Vascular Pharmacology, 2006
The limitations of surgical revascularisation and pharmacological treatment in peripheral arterial occlusive disease (PAOD) are well recognized. Therapeutic options for critical leg ischemia are consequently limited to percutaneous transluminal angioplasty (PTA) or surgical revascularisation. Unfortunately, many patients with critical leg ischemia are poor candidates for either procedure. Therapeutic angiogenesis is a novel promising tool to treat these patients. Experimental and clinical and trials of gene transfer for therapeutic angiogenesis have already shown some clinical efficacy. This review is focused on gene transfer techniques in preclinical and clinical therapeutic angiogenesis, angiogenic growth factors, vectors, delivery methods and routes. The results of clinical and experimental studies, safety and side effects of gene therapy, and the perspectives of future research are also discussed.
Gene-based therapies in patients with critical limb ischemia
Expert Opinion on Biological Therapy, 2017
Introduction: Critical limb ischemia (CLI) constitutes a life-limiting and life-threatening disease. Revascularization, either endovascular or surgical, remains the best treatment option accompanied by medication and risk factor modification. Patients unable to undergo revascularization, referred as "no-option patients", have been the center of interest the last few years, subjected to treatment therapies based on proteins (mainly growth factors) involved in angiogenesis via gene delivery to the ischemic tissue. Areas Covered: This review focuses on these growth factors, gives an update of the studies available, discusses the possible problems that influence outcomes and describes future perspectives including possible new technologies that will improve them. Additionally, the authors attempt to place therapeutic angiogenesis to the bigger frame of tailored therapy in CLI. Expert opinion: Although encouraging in the beginning, growth factor therapy results have been equivocal and inconclusive. And while it would be misleading to approach gene therapy as panacea, its effect on the micro-circulatory level activating angiogenesis and arteriogenesis could act as an important adjunct in personalized treatment.
Molecular Therapy, 2010
Generation of novel therapeutic modalities for the clinical problem of critical limb ischemia is clearly warranted by the substantial impact this condition has on morbidity and mortality, as well as on the paucity of existing effective treatment options. 1 In this context, our laboratory 2,3 and others 4,5 have investigated the potential utility of intra-arterial gene transfer of endothelial nitric oxide synthase (eNOS) into an ischemic limb as a therapeutic intervention designed to improve perfusion and minimize tissue loss.
PLoS ONE, 2011
Background: Induction of neovascularization by releasing therapeutic growth factors is a promising application of cellbased gene therapy to treat ischemia-related problems. In the present study, we have developed a new strategy based on nucleofection with alternative solution and cuvette to promote collateral growth and re-establishment of circulation in ischemic limbs using double transplantation of gene nucleofected primary cultures of fibroblasts, which were isolated from rat receiving such therapy.
Current Neurovascular Research, 2011
The present clinical trial analyzed the safety of gene therapy using plasmidial constructs expressing vascular endothelial and hepatocyte growth factors in patients with critical limb ischemia. The study included 43 patients: 29 in the treatment group and 14 allocated to the placebo group. The primary end points were the rate of major amputations and the clinical safety of the method. Secondary end points were improvement of pain at rest, walking ability and the ankle/brachial pressure index. The overall major amputation rate was 31.04% in the treatment group and 71.42% in the placebo group (p=0.029). Pain at rest was improved in 65% of patients in the gene therapy group and in 7% in the placebo group (p=0.0006). There were no significant adverse effects in the treatment group. Conclusion: Gene therapy with vascular endothelial and hepatocyte growth factors is therapeutically safe and reduces the rate of major amputations and relieves pain at rest in patients with critical limb ischemia.