Ryu Ji-Kan, Suh Jun-Kyu, Burnett Arthur L
National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 400-711, Korea.
Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Transl Androl Urol. 2017 Apr;6(2):207-215. doi: 10.21037/tau.2016.11.17.
Although oral phosphodiesterase-5 (PDE5) inhibitors are generally accepted as an effective therapy for erectile dysfunction (ED), men with ED from diabetes or radical prostatectomy respond poorly to these drugs. Many researchers have tried to develop novel therapeutics that target alternative molecular pathways. A group of therapeutics belongs to centrally acting agents that target dopamine and melanocortin receptors. The other one is the peripherally acting agents that target soluble guanylate cyclase, Rho-kinase pathway, and Maxi-K channel, etc. Also, a variety of preclinical studies by the application of biotherapies in the concept of therapeutic angiogenesis or neural regeneration as well as anti-fibrosis to regenerate damaged erectile tissue have been reported. This article will address the current therapeutic targets for ED under clinical or preclinical development, including pharmacotherapy and biotherapy which comprises protein therapy and gene therapy. In spite of numerous clinical trials that target alternative pathways, these agents have yet to reach the market. The results from preclinical studies targeting therapeutic angiogenesis, neural regeneration, and anti-fibrosis are promising.
尽管口服磷酸二酯酶-5(PDE5)抑制剂通常被认为是治疗勃起功能障碍(ED)的有效疗法,但患有糖尿病或接受根治性前列腺切除术所致ED的男性对这些药物反应不佳。许多研究人员试图开发针对其他分子途径的新型疗法。一类疗法属于作用于中枢的药物,靶向多巴胺和黑皮质素受体。另一类是作用于外周的药物,靶向可溶性鸟苷酸环化酶、Rho激酶途径和大电导钙激活钾通道等。此外,已有多项临床前研究报道了应用生物疗法,从治疗性血管生成或神经再生以及抗纤维化的概念出发,来再生受损的勃起组织。本文将探讨目前处于临床或临床前开发阶段的ED治疗靶点,包括药物治疗和生物治疗,生物治疗包括蛋白质治疗和基因治疗。尽管针对其他途径进行了大量临床试验,但这些药物尚未上市。针对治疗性血管生成、神经再生和抗纤维化的临床前研究结果很有前景。