Multidisciplinary Approach to Treat Erectile Dysfunction

Erectile dysfunction (ED) is a widespread disease affecting approximately 20% of men. With a rising incidence due to the global ageing of the world population, it is estimated that over 322 million patients will be affected in 2025. While not being a lifethreatening disease, ED has a strong detrimental impact on the patientâ s quality of life, commonly leading to a reduction of work productivity, anxiety, chronic stress, depression or loss of self-esteem. Despite all the recent advances in understanding the molecular mechanisms and pathophysiology of ED, and the discovery of effective oral treatments that are the PDE5 inhibitors (such as Viagra®), there is still an important portion of the population that does not respond to this therapy. Therefore, they unfortunately resort on problematic, uncomfortable, and invasive last-resort solutions due to the lack of better alternatives. In addition, current treatments are inducing assisted erection rather than handling the root cause of the disease. Considering the limited number of strategies currently existing for the treatment of ED and their drawbacks, there is an urgent need for alternative therapies. Due to the fact that both vascular and neural components are required to induce and maintain a satisfactory erectile response, as well as the multifactorial origins of ED, new therapies able to combine multidisciplinary approaches would increase the chances of new treatment success. Therefore, this thesis focuses on different multidisciplinary strategies attempting to provide novel therapies to alleviate ED or its causes. In the first part of this thesis, we have investigated the anti-fibrotic capabilities of a vasoactive endogenous peptide called Apelin-13 on a mouse model of ED, providing promising results and pointing out Apelin as a candidate for the development of fibrosis-associated ED treatments. Secondly, we have developed a novel concept enabling the neurostimulation of the cavernous nerves (CN) to induce penile erection. This thesis shows the first intraoperative proof of principle in humans, opening the way for the development of an innovative medical device for the neuromodulation of erectile function to treat neurogenic ED. Finally, we have studied further the effects of CN low-intensity electrostimulation (LIES), another application of nerve electrical stimulation, with the potential of promoting CN regeneration. We observed a significant protective effect of LIES on penile tissue structure and functions following nerve trauma in a rat model of cavernous nerve injury. Altogether, the work underwent in this thesis add to the development of more effective and comfortable treatment options to alleviate ED, which could not only improve the quality of life of patients but could also reduce the burden and cost this disease places on medical and public health systems.