Therapy of erectile dysfunction: potential future treatments.

Current research on the development of new medical treatments of erectile dysfunction (ED) fall essentially into two main types of approaches: (1) the traditional strategy based on compounds acting to induce an erection on demand, without modifying the underlying pathologic alterations that lead to ED; and (2) more novel agents not inducing an erectile response but aiming for a long-term correction of either the defect in cavernosal tissue integrity responsible for functional impairment, or the impairment per se of the cavernosal tissue function. In the first approach, new phosphodiesterase inhibitors (either more potent and specific than the clinically available ones or harboring nitric oxide-releasing structures), soluble guanylate cyclase activators, Rho kinase inhibitors, as well as centrally active agents stimulating hypothalamic dopamine or melanocortin receptors, combinations of different types of drugs, and new facilitators of tissue uptake of active agents, are being investigated and some may soon be applied clinically. In the second approach, the first type of correction comprises regulators of endogenous cell number and integrity and extracellular matrix turnover (inhibitors of apoptosis and fibrosis, neurotrophic and angiogenic factors), testosterone, and tissue and cell explants (nerve and smooth muscle grafting, adult pluripotent cells), whereas the second includes in vivo gene therapy with different genes and vectors, and ex vivo gene therapy, combining gene transfer with stem cell implants. This second approach requires extensive laboratory research prior to clinical translation but may provide a means to cure ED. The current status and future directions of these strategies are discussed.