Introduction: Erectile dysfunction (ED) has reached epidemic proportions not expected to abate because of population aging and chronic diseases that accompany advanced age. Vasculopathy is a main cause, but damage to penile innervation also underlies many cases of ED. Phosphodiesterase inhibitor therapies do not help all men with ED, making the search for novel therapeutic drug and treatment targets of utmost importance. Aims: To review the literature to identify potential new treatment targets to fill a gap in therapeutic options for men with ED, with a focus on treatments for vasculogenic ED, but including novel treatment targets for ED due to penile nerve damage, a frequent consequence of pelvic surgery in men. Methods: The recent literature was searched for publications on in vitro, in vivo, pre-clinical and observational human studies, when available, that would identify potential new targets for ED therapies not previously, or not extensively reviewed. Results: Literature searches identified microparticles, myeloperoxidase, and heme oxygenase-1 as emerging molecular targets to treat vasculogenic ED. Novel regenerative therapy targets, including sonic hedgehog, galanin, and cell-based treatments were also reviewed as potential future treatments for ED due to damage to penile innervation. Conclusion: Novel molecular targets and cell-based therapies offer great hope for advances in ED treatment. Concerns regarding efficacy, toxicity, off target effects, safety, and convenience apply to these targets; much work remains to confirm these as viable targets to pursue for effective ED treatments. To complement targets discussed in this review relevant review papers were cited for the interested reader. To complement targets discussed in this review relevant review papers were cited for the interested reader
Keywords: Erectile dysfunction, heme oxygenase-1, microparticles, myeloperoxidase, platelets, regenerative therapies, vascular inflammation.