#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

GENE THERAPY - NEW HOPE FOR THE TREATMENT OF ERECTILE DYSFUNCTION?


Authors: MUDr. Libor Zámečník;  Febu
Authors‘ workplace: Urologická klinika 1. LF UK a VFN
Published in: Urol List 2007; 5(3): 34-37

Overview

Current available treatment options for erectile dysfunction (ED) are effective but not without failure and/or side effects. Although the development of phosphodiesterase type 5 (PDE5) inhibitors (i.e. sildenafil, tadalafil and vardenafil) has revolutionized the treatment of ED, these oral medications required on-demand are less efficacious in some hard-to-treat populations (diabetics, men after radical prostatectomy). Recent trials have demonstrated that gene therapy strategies may be applicable for such purposes. Improvement in the treatment of ED depends on the understanding of the regulation of human corporal smooth muscle tone and on the identification of relevant molecular targets. Tissue engineering and gene therapy are currently investigated in animal studies for reconstructing penile tissue or treating erectile dysfunction. Future ED therapies might consider the application of molecular technologies, such as gene the­rapy. As a potential therapeutic tool, gene therapy might provide an effective and specific means of altering intracavernous pressure "on demand" without affecting the other penile functions. Gene therapy is applicable to the penis because of its location and accessibility, low penile circulatory flow in flaccid state and the presence of endothelial lined lacunar spaces. Gene therapy approaches have focused on a number of signalling pathways that are crucial for penile erection (i.e. nitric oxide/cyclic guanosine monophosphate, RhoA/Rho-kinase, growth factors, ion channels, peptides). This review provides a brief insight of the current role of gene therapy in the management of ED.

Key words:
gene therapy, erectile dysfunction


Sources

1. Vonka V. Genová terapie v onkologii. Sanquis 2004; 6: 32.

2. Gaston KE, Ornstein DK. Pharmacotherapy for biochemical recurrences after therapy for localised prostate cancer. Expert Opin Pharmacother 2002; 3: 657-669.

3. Kendirci M, Teloken PE, Champion HC et al. Gene therapy for erectile dysfunction: fact or fiction? Eur Urol 2006; 50: 1208-1222.

4. Song LJ, Pan LJ, Xu YM. Reconstruction of penile function with tissue engineering techniques. Zhonghua Nan Ke Xue 2007; 13: 352-355.

5. Kendirci M, Gur S, Sikka SC. Gene therapy for erectile dysfunction. Front Biosci 2005; 10: 2758-2769.

6. Bivalacqua TJ, Champion HC, Mehta YS et al. Adenoviral gene transfer of endothelial nitric oxide synthase (eNOS) to the penis improves age-related erectile dysfunction in the rat. Int J Impot Res 2000; 12(suppl 3): S8-17.

7. Xing JP, Sun JH, Cui XF, Qiu SD. Expression and effect of hCGRP recombinant adeno-associated virus in primary cultured corporal cavernosum smooth muscle cells of the rat in vitro. Zhonghua Nan Ke Xue 2005; 11: 918-921.

8. Melman A. Gene transfer for the therapy of erectile dysfunction: progress in the 21st century. Int J Impot Res 2006; 18: 19-25.

9. Lee M, Ryu JK, Oh SM et al. Water-soluble lipopolymer as a gene carrier to corpus cavernosum. Int J Impot Res 2005; 17: 326-334.

10. Yetik-Anacak G, Catravas JD. Nitric oxide and the endothelium: history and impact on cardiovascular disease. Vascul Pharmacol 2006; 45: 268-276.

11. Bivalacqua TJ, Usta MF, Champion HC et al. Gene transfer of endothelial nitric oxide synthase partially restores nitric oxide synthesis and erectile function in streptozotocin diabetic rats. J Urol 2003; 169: 1911-1917.

12. Bivalacqua TJ, Usta MF, Champion HC et al. Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats. Int J Impot Res 2004; 16: 21-29.

13. Davila HH, Magee TR, Vernet D et al. Gene transfer of inducible nitric oxide synthase complementary DNA regresses the fibrotic plaque in an animal model of Peyronie´s disease. Biol Reprod 2004; 71: 146-151.

14. Gonzales-Cadavid NF, Burnstock G, Magee TR et al. Expression of penile neuronal nitric oxide synthase variants in the rat and mouse penile nerves. Biol Reprod 2000; 63: 704-714.

15. Xie Y, Garbar C, Ng C et al. Effect of long-term passive smoking on erectile function and penile nitric oxide synthase in the rat. J Urol 1997; 157: 1121-1126.

16. Christ GJ. K+ channels and gap junctions in the modulation of corporal smooth muscle tone. Drug News Perspect 2000; 13: 28-36.

17. Christ GJ, Melman A. The application of gene therapy to the treatment of erectile dysfunction. Int J Impot Res 1998; 10: 111-112.

18. Christ GJ, Day N, Santizo C et al. Intracorporal injection of hSlo cDNA restores erectile capacity in STZ-diabetic F-344 rats in vivo. Am J Physiol Heart Circ Physiol 2004; 287: 1544-1553.

19. Melman A, Bar-Chama N, McCullough A et al. The first human trial for gene transfer therapy for the treatment of erectile dysfunction: preliminary results. Eur Urol 2005; 48: 314-318.

20. Melman A, Bar-Chama N, McCullough A et al. hMaxi-K gene transfer in males with erectile dysfunction: results of the first human trial. Hum Gene Ther 2006; 17: 1165-1176.

21. Gholami SS, Rogers R, Chang J et al. The effect of vascular endothelial growth factor and adeno-associated virus mediated brain derived neurotrophic factor on neurogenic and vasculogenic erectile dysfunction induced by hyperlipidemia. J Urol 2003; 169: 1577-1581.

22. Rogers RS, Graziottin TM, Lin CS et al. Intra­ca­ver­nosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGF gene therapy prevent and reverse venogenic erectile dysfunction in rats. Int J Impot Res 2003; 15: 26-37.

23. Seftel A. Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGF gene therapy and reverse venogenic erectile dysfunction in rats. J Urol 2003; 170: 681.

24. Cormio L, Gesualdo L, Maiorano E et al. Vaso­active intestinal polypeptide (VIP) is not an androgen-dependent neuromediator of penile erection. Int J Impot Res 2005; 17: 23-26.

25. Champion HC, Wang R, Santiago JA et al. Compa­rison of responses to adrenomedullin and calcitonin gene-related peptide in the feline erection model. J Androl 1997; 18: 513-521.

26. Moore CR, Wang R. Pathophysiology and treatment of diabetic erectile dysfunction. Asian J Androl 2006; 8: 675-684.

27. Jin L, Liu T, Lagoda GA et al. Elevated RhoA/Rho-kinase activity in the aged rat penis: mechanism for age-associated erectile dysfunction. Faseb J 2006; 20: 536-538.

Labels
Paediatric urologist Urology
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#