Gene therapy for erectile dysfunction: fact or fiction?
OBJECTIVE
Erectile dysfunction (ED) is a major health problem that seriously affects the quality of life of patients and their partners. Although all three selective phosphodiesterase type 5 inhibitors (PDE5-Is) are effective in the majority of ED cases, PDE5-I therapy is less efficacious in some hard-to-treat populations (diabetics, men after radical prostatectomy), prompting the development of new approaches, including gene therapy strategies for ED.


METHODS
Gene therapy approaches are discussed in terms of the possible role of gene therapy for the treatment of ED, potential targets for gene transfer, vectors to carry targeted genes, and gene strategies for ED in certain disease states, such as diabetes, ageing, arterial and venogenic insufficiency, and cavernous nerve injury.


RESULTS
The penis is a convenient tissue target for gene therapy because of its external location and accessibility, the ubiquity of endothelial-lined spaces, and low level of blood flow, especially in the flaccid state. Gene therapy approaches have focused on a number of signaling pathways that are crucial for penile erection, such as nitric oxide/cyclic guanosine monophosphate, RhoA/Rho-kinase, growth factors, ion channels, peptides, and control of oxidative stress.


CONCLUSIONS
The need for effective ED therapies in difficult-to-treat patients has encouraged investigators to seek novel modalities for the treatment of ED. Recent preclinical and clinical trials have demonstrated that gene therapy strategies may be feasible for these purposes.
Kendirci
Muammer
M
Department of Urology, Sisli Etfal Training and Research Hospital, Istanbul, Turkey.
Teloken
Patrick E
PE
Champion
Hunter C
HC
Hellstrom
Wayne J G
WJ
Bivalacqua
Trinity J
TJ
D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D007172:Erectile Dysfunction / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D010410:Penile Erection / Q000502:physiology; D016896:Treatment Outcome