Gene therapy ischemia

Thee future prospects for naked DNA gene therapy include clinical trials for genetic diseases (e.g., Duchenne muscular dystrophy, ischemia, hemophilia), which would be initiated in the next few years, and tail vein injections in rodents, which will become a widely used technique for rapidly testing expression vectors/gene therapy approaches (101). 

Nanoparticles formulated with PLGA have been shown to be rapidly uptaken by the endothelial cells, the uptake was shown to depend on the nanoparticle concentration and the particles where mainly shown to localize in the cytoplasm (207). These nanoparticles were also shown to be biocompatible with the cells with no effect on cell viability (207). This is important due to the fact that endothelium is an important target for gene therapy in a number of disorders including angiogenesis, atherosclerosis, tumor growth, myocardial infarction, limb and cardiac ischemia, restenosis (207). 

Gene therapy provides an alternative to amputation and heart transplant for the treatment of ischemia. The focus of gene therapy for ischemia has been on genes for angiogenic growth factor and fibroblast growth factor where the goal is to deliver... 

Hermonat PL, Mehta JL. 2004. Potential of gene therapy for myocardial ischemia. Curr Opin Cariol. 19 517-523. 

Tsai TH, Chen SL, Xiao X, Chiang YH, et al. 2006. Gene therapy of focal cerebral ischemia using defective recombinant adeno-associated virus vectors. Front Biosci. 11 2061-2070. 

Losordo, D.W., Vale, P.R., Symes, J.F., Dunnington, C.H., Esakof, D.D., Maysky, M. et al. (1998) Gene therapy for myocardial angiogenesis initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation, 98, 2800-2804. 

Jayakumar, J., Suzuki, K., Khan, M., Smolenski, R.T., Farrell, A., Latif, N. et al. (2000) Gene therapy for myocardial protection Transfection of donor hearts with heat shock protein 70 gene protects cardiac function against ischemia-reperfiision injury. Circulation, 102 (19 Suppl. 3), III302-306. 

Masaki I, Yonemitsu Y Yamashita A, et al. Angiogenic gene therapy for experimental critical limb ischemia acceleration of limb loss by overexpression of vascular endothelial growth factor 165 but not of fibroblast growth factor-2. Circ Res 2002 90(9) 966-973,... 

III. Transplantation of Neural Stem Cells and Gene Therapy in the Brain Ischemia... 

Our studies support the hypothesis that cardiac cell membrane lesion sealing with CSIL result in preservation of myocardial viability, as determined by function, histochemistry, and ultra-structural morphology. There is a time response to myocardial preservation with CSIL therapy. Early CSIL intervention after the onset of ischemia resulted in almost complete myocardial recovery (18). Even when the intervention was initiated at 20 min of global ischemia, myocardial preservation was still greater than that seen in hearts with IgG-L or placebo treatment. There is also a dose response to CSIL therapy. Sufficient concentration of CSIL is essential to achieve optimal cell membrane lesion sealing (I9).Therefore, CSIL therapy may find therapeutic applications in preservation of myocardial viability and efficient non-viral gene therapy. 

Delivery of gene transfer systems of heat shock proteins (Hsp70),250 antioxidant enzymes (catalase)251 or survival genes (Akt)252 has been associated with myocardial protection against ischemia and reperfusion. A vector gene therapy system has also been developed with a hypoxia response element-incorporated promoter to turn on the gene expression in response to hypoxic signal.253... 

Y. Tang, M. Jackson, K. Qian and M.I. Phillips, Hypoxia inducible double plasmid system for myocardial ischemia gene therapy, Hypertension 39(2), 695-698 (2002). 

Adenovirus-based Gene Therapy Therapeutic Angiogenesis with Adenovirus 5 Fibroblast Growth Factor-4 (Ad5FGF-4) in Patients with Chronic Myocardial Ischemia... 

---