Gene therapy and erectile dysfunction: the current status.
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 require on-demand access and are not as effective in treating ED related to diabetic, post-prostatectomy and severe veno-occlusive disease states. Improvement in the treatment of ED is dependent on understanding the regulation of human corporal smooth muscle tone and on the identification of relevant molecular targets. 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 for altering intracavernous pressure "on demand" without affecting resting penile function. However, the safety of gene therapy remains a major hurdle to overcome before being accepted as a mainstream treatment for ED. Gene therapy aims to cure the underlying conditions in ED, including fibrosis. Furthermore, gene therapy might help prolong the efficacy of the PDE5 inhibitors by improving penile nitric oxide bioactivity. It is feasible to apply gene therapy to the penis because of its location and accessibility, low penile circulatory flow in the flaccid state and the presence of endothelial lined (lacunar) spaces. This review provides a brief insight of the current role of gene therapy in the management of ED.
Lau
David H W
DH
Department of Urology, Royal Free Hospital and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2QG, UK. htpdlau@aol.com
Kommu
Sashi S
SS
Siddiqui
Emad J
EJ
Thompson
Cecil S
CS
Morgan
Robert J
RJ
Mikhailidis
Dimitri P
DP
Mumtaz
Faiz H
FH
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000627:therapeutic use
D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human