Gene therapy and erectile dysfunction: The current status

D. H. W. Lau^1,2,3,4, S. S. Kommu ⁵, E. J. Siddiqui ^2,3,4, C. S. Thompson^2,3, R. J. Morgan¹, D. P. Mikhailidis^2,3, F. H. Mumtaz^4
1Department of Urology, Royal Free Hospital and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK
²Department of Clinical Biochemistry, Royal Free Hospital and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK
³Department of Surgery, Royal Free Hospital and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK
⁴Department of Urology, Chase Farm Hospital, The Ridgeway, Enfield EN2 8JL, UK
⁵Institute of Cancer Research and The Royal Marsden Hospitals NHS Foundation Trust, Surrey, UK
DOI: 10.1111/j.1745-7262.2006.00224.x

Abstract
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 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 phosphodiesterase type 5 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.
Keywords: gene therapy; nitric oxide synthase; erectile; calcium-sensitive potassium channel; vascular endothelial growth factor; calcitonin gene-related peptide

Correspondence to: Prof. David H. W. Lau, Department of Clinical Biochemistry, Royal Free Hospital, Pond Street, London, NW3 2QG, UK.
Tel: +44 207 830 2258, Fax: +44 207 830 2235
E-mail: htpdlau@aol.com
Received 2006-01-26 Accepted 2006-06-16