Gene and Stem Cell Therapy in Erectile Dysfunction

Erectile dysfunction (ED) is a complex, multifactorial issue commonly affecting men of all ages. ED is currently defined as “the inability to achieve and/or maintain penile erection sufficient to permit satisfactory sexual intercourse”, and has been associated with such risk factors as hypertension, diabetes, alcoholism, smoking, and pelvic surgery [1]. This condition has seriously impacted the men’s quality of life. Even though nowadays there are a large number of options to treat ED, a considerable number of patients do not answer adequately the conventional therapies available. Penile erection is achieved through a neurovascular response exhibiting an increase in arterial inflow, relaxation of corporal smooth muscle, and restriction of the venous outflow. Relatively recent pharmacological advances, namely oral phosphodiesterase-5 (PDE5) inhibitors, have become the first line of treatment in ED. PDE5 inhibitors allow the patient to achieve a penile erection via the effects on the nitric oxide (NO) signaling pathway, which is the principal mediator of corporal smooth muscle relaxation. The inhibition of the degradative actions of PDE5 on 3’,5’-cyclic guanosine monophosphate (cGMP), the second messenger molecule of NO signaling, lead to an increased bioavailability of NO in the corporal smooth muscle thus promoting vasodilation and penile erection. However, despite the widespread efficacy of these medications, there are still men for which oral PDE5 inhibitors are ineffective. ED in men with diabetes, for example, is typically more severe, exhibiting a less effective response to PDE5 inhibitors when compared to non-diabetic patients. The vascular injuries that accompanies diabetes is often too damaging to endothelial physiology to allow adequate penile erections [4] and thus complicates use of the oral medications as treatment for ED. Due to the vast array of potential causes of ED ranging from neurogenic and vasculogenic to hormonal issues, there exists a continuing need to address these deficiencies in patient management of ED and pursue new treatments. Two avenues showing a great deal of promise in ED treatment are gene therapy and stem cell therapy, both of which could possibly provide methods to prevent or even cure ED. This chapter will focus on recent studies in both gene and stem cell therapies in ED research, with the objective to establish that continued scientific exploration into these fields will yield clinically applicable approaches to combat this condition.