Gene Therapy for Erectile Dysfunction / 대한남성과학회지

ABSTRACT

It is now well known that vascular diseases, including hypercholesterolemia, atherosclerotic vascular disease, and diabetes mellitus are major causes for erectile dysfunction(ED). Despite the introduction of oral phosphodiesterase-5 inhibitors in the treatment of ED, new therapeutic strategies are warranted. Current therapies have two shortcomings. First, every currently approved non-surgical treatment option for ED requires planning prior to intercourse. Second, there is a need for increased treatment efficacy for patients with moderate to severe ED. Gene therapy may well address both of these areas, as the ultimate goal of the therapy is the restoration of physiologic erections following normal endogenous signals, in the absence of the any other form of therapy. The penis is a convenient organ for local gene therapy because of its external location, ubiquity of endothelial-lined spaces, slow circulation in the flaccid state, and gap junctions between smooth muscles, which ensure wide distribution of injected genes inside the penis. Many gene therapy approaches have focused on the NO/cGMP pathway, angiogenic factors, neurotrophic factors, potassium channels, the RhoA/Rho-kinase system, etc. Various viral and nonviral vectors as well as genetically engineered cells have been used as gene delivery vehicles for the transfer of genetic material to the target cell or tissues. In contrast to its use in cancer, the application of gene therapy for a non-life threatening disease, such as ED, requires a higher safety level and more knowledge of secure and efficacious vectors for gene transfer. The preclinical data from recent studies in several ED models are quite impressive and encouraging. Gene therapy interventions to restore erectile function may represent an exciting new therapeutic strategy for the future treatment of ED.