Terapia gênica com VEGF para angiogênese na angina refratária: ensaio clínico fase I/II

Abstract

Objective: To evaluate the safety, feasibility and initial and clinical effects on myocardial perfusion, intramyocardial, transthoracic administration of plasmid VEGF 165 in patients with advanced coronary artery disease and refractory angina, which are not qualified for percutaneous revascularization and surgery.Methods: A cohort study phase I. Thirteen patients with ischemic heart disease refractory angina despite maximum medical treatment for at least six months, not qualifying for surgical or catheter underwent intramyocardial injection of VEGF 165 plasmid 2000ìg. Patients were evaluated by myocardial scintigraphy, exercise testing, quality of life questionnaire (Minnesota) and determining the classes of heart failure (NYHA) and angina (CCS).Results: There were no deaths or recurrences. During the period of maximum medical treatment, there was no difference in myocardial scintigraphy, exercise stress tests and questionnaires on quality of life also found a trend towards worsening of NYHA class (P = 0.05) and CCS (P = 0.05) . Three months after intervention we observed improvements in scintigraphic SSS scores (18.38 ± 7.51 vs. 15.31 ± 7.29, P = 0.003) and SRS (11.92 ± 7.49 vs. 8.53 ± 6.68, P = 0.002) but not in proportion to the areal extent of ischemic Rev Bras Cir Cardiovasc 2010; 25(3): 311-321 of administration of VEGF. Clinical trials bring controversial results, many showing evidence of clinical improvement and angiogenesis [8][9][10][11][12][13][14][15][16][17][18][19] and others showing no differences in myocardial perfusion when compared to their controls [7,20]. Thus, although promising, remain still not completely clear the clinical effects on the myocardium vascularization of the therapy with VEGF in its various forms and ways of administration, justifying further studies. KALIL, RAK ET AL -VEGF gene therapy for angiogenesis in refractory angina: clinical trial phase I/IIThis clinical assay aims to evaluate the safety, feasibility and initial clinical effects (featuring a clinical assay phase I / II), under myocardial perfusion, intramyocardial, transthoracic administration of plasmid VEGF 165 in patients with advanced CAD and refractory angina, which are not qualified for surgery and percutaneous revascularization. We emphasize that we used for the first time, a plasmid entirely produced in Brazil.

Gene Therapy in Cardiac Surgery: Clinical Trials, Challenges, and Perspectives

“…Minithoracotomy with intramyocardial (transepicardial) gene delivery was used several more times in clinical trials in patients who were not candidates for future direct revascularization because of diffuse disease with poor runoff vessels, lack of available conduits, or high operative risks [19–23]. The next step was intramyocardial (transendocardial) injections performed percutaneously in conjunction with the catheter-based LV electromechanical three-dimensional mapping system NOGA [24–27] or a Myostar mapping injection catheter [28].…”

Perspectivas da terapia gênica

“…No caso de terapia gênica, pesquisadores brasileiros já realizaram protocolos clínicos envolvendo transferência gênica com vetores não-virais e têm participado em protocolos multicêntricos internacionais [38][39][40][41] . Os próprios pesquisadores neste campo tem se organizado em rede, como é o caso do Instituto do Milênio (2005Milênio ( -2008, INCT (Instituto Nacional de Ciência e Tecnologia, aprovado no mérito, 2010) e com recentes propostas ao INCT que atualmente está em análise (dezembro/2015).…”

Terapia gênica para cardiopatia isquêmica

“…Current tests report that the use of high doses of VEGF, compared with low doses and placebo, improves myocardial perfusion in patients with severe angina and provides evidence of a dose-dependent positive effect [46.47]. Confronted with evidence, VEGF has been shown to be a potential angiogenic factor, which benefits in medium and long term follow-up have been or are being assessed, including the improvement of quality of life, functional class of heart failure, angina class, functional capacity and reduction of myocardial ischemia [25,28,45,46,[48][49][50][51][52][53][54][55][56][57].…”

“…In the Cardiology Institute of RS/FUC and the Discipline of Cardiology of UFCSPA, in collaboration with the Laboratory of Immunogenetics, UFRGS, we previously developed experimental studies [65][66][67] and recently performed the first gene therapy clinical trial in Brazil, using VEGF165 for refractory angina [53].…”

“…Recently, we developed a controlled clinical trial, phase I/II (ClinicalTrial NCT00744315) [53] in order to clinically assess the effects of gene therapy with VEGF165 in patients with advanced coronary artery disease (CAD), not eligible for revascularization or percutaneous surgical. The thirteen patients received optimal drug therapy for at least six months and underwent administration of intramyocardial injections of 2000 µg of plasmid VEGF 165 .…”