Preclinical and clinical experience in vascular gene therapy: advantages over conservative/standard therapy.
No systemic pharmacological treatment has been shown to convincingly reduce the incidence of restenosis after angioplasty or increase the formation of collaterals in ischemic tissue in patients. The lack of success of many pharmaceutical agents in reducing restenosis rates or in inducing angiogenesis post-angioplasty and following stent implantation has encouraged the development of new technological treatment approaches. Gene therapy is a novel strategy with the potential to prevent some of the sequelae after arterial injury, particularly cell proliferation, and to induce growth of new vessels or remodeling of pre-existing vessel branches, which may help patients with critical ischemia. Gene therapy strategies have the advantage of minimizing systemic side effects and may have a long-term effect as the encoded protein is released. Most clinical trials investigating gene therapy for vascular disease have been uncontrolled phase I and IIa trials. Gene therapy into vessels with the genes for growth factors has been demonstrated to be feasible and efficient. Local drug delivery devices have been used in combination with gene therapy in several trials to maximize safety and efficiency. Data from experimental animal work indicates that gene therapy may modify intimal hyperplasia after arterial injury, but there are few clinical trials on restenosis in patients. Preliminary clinical results show only limited success in altering restenosis rates. In vitro and experimental in vivo investigations into gene therapy for angiogenesis demonstrate increased formation of collaterals and functional improvement of limb ischemia. There is some evidence of increased collateral formation and clinical improvement in patients with critical limb ischemia. Results of placebo-controlled and double-blind trials of gene therapy for vascular disease are awaited.
Nikol
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Medical Department I, Klinikum Grosshadern, Marchioninistr 15, D-81377 Munich, Germany. s-nikol@gmx.de
Huehns
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D002986:Clinical Trials as Topic; D003097:Collateral Circulation; D003251:Constriction, Pathologic / Q000517:prevention & control; D016228:Endothelial Growth Factors / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007511:Ischemia / Q000628:therapy; D008222:Lymphokines / Q000235:genetics; D020033:Protein Isoforms; D012008:Recurrence; D014652:Vascular Diseases / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors