Lau David H W, Kommu Sashi S, Siddiqui Emad J, Thompson Cecil S, Morgan Robert J, Mikhailidis Dimitri P, Mumtaz Faiz H
Department of Urology, Royal Free Hospital and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2QG, UK.
Asian J Androl. 2007 Jan;9(1):8-15. doi: 10.1111/j.1745-7262.2007.00224.x. Epub 2006 Aug 4.
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.
勃起功能障碍(ED)目前可用的治疗方法是有效的,但并非没有失败和/或副作用。尽管5型磷酸二酯酶(PDE5)抑制剂(即西地那非、他达拉非和伐地那非)的开发彻底改变了ED的治疗方式,但这些口服药物需要按需服用,并且在治疗与糖尿病、前列腺切除术后和严重静脉闭塞性疾病相关的ED方面效果不佳。ED治疗的改善取决于对人体海绵体平滑肌张力调节的理解以及相关分子靶点的识别。未来的ED治疗可能会考虑应用分子技术,如基因治疗。作为一种潜在的治疗工具,基因治疗可能提供一种有效且特异的方法,可“按需”改变海绵体内压力,而不影响阴茎的静息功能。然而,在被接受为ED的主流治疗方法之前,基因治疗的安全性仍然是一个需要克服的主要障碍。基因治疗旨在治愈ED的潜在病症,包括纤维化。此外,基因治疗可能通过改善阴茎一氧化氮生物活性来帮助延长PDE5抑制剂的疗效。由于阴茎的位置和可及性、疲软状态下阴茎循环血流量低以及存在内皮衬里(腔隙性)空间,将基因治疗应用于阴茎是可行的。本综述简要介绍了基因治疗在ED管理中的当前作用。