The Treatment of Erectile Dysfunction in Patients With Neurogenic Disease

Anand N. Shridharani; William O. Brant


Transl Androl Urol. 2016;5(1):88-101. 

In This Article

Future Directions

Since the advent of PDE5i, many other selective and non-selective peripheral acting compounds have been developed or are in development. Avanafil has shown promising results in treating ED in post-prostatectomy patients with suspected cavernous nerve injury.[111] Other PDE5i marked in Asia such as udenafil, and mirodenafil also effective at treating ED may minimize side effects due to shorter half-lives.[112–114] Soluable guanylate-cyclase inhibitors and potassium channel activators are compounds that have induced erections in animal models but remain experimental requiring further investigation.[115–117]

Centrally active compounds such as apomorphine have been used in men with ED whose cardiovascular comorbidity may prohibit PDE5i use, or in men who have concurrent apomorphine use for its anti-parkinsonian properties. Unfortunately, its side effect profile and poor effectiveness compared to other ED treatments have impaired its mainstream utilization.[118] It is suspected that the side effects of apomorphine relate to its D2 receptor affinity. D4 receptor agonists, such as ABT-724 and azulenylmethylpiperazines, may not have the same associated side effects and show potent pro-erectile effects in animal models compared to apomorphine.[32,119]

Melanocortin receptor agonists were found to induce erections serendipitously. A study investigating the dermatologic use of Melanotan-II (MT-II) was found to generate erections unexpectedly leading to the development of MTII derivatives for ED treatment.[120] MT-II was initially used to induce pigment changes in the skin for artificial tanning but has been suspected to induce melanoma, however.[121]

Finally, gene therapy and stem cell research has widened the frontier of ED treatment proposed as possibility to even reverse ED. Specifically, gene therapy pertains to repairing the cause of ED by restoring defective gene function and/or altering the expression of the mutant gene.[32] Most of the available data on gene therapy are in the animal model. However, a phase I clinical trial in men with ED undergoing intracavernous injection with a DNA plasmid carrying the alpha-subunit of the corporal smooth muscle Maxi-K channel showed promise in increased erectile function based on IIEF assessment sustained throughout the 3-month study period.[122]

Recently, several advances in the uses of stem cells have bet met with great anticipation. Stem cells have the ability to differentiate into different cell lines based on the cellular signaling they receive. Bone marrow mononuclear cells in particular have been used for the treatment of ED in animal models. Yiou et al. recently delivered bone marrow-mononuclear cells (BM-MNC) into the intracavernous smooth muscle of post radical prostatectomy men.[123] The open label, dose escalation phase I/II trial showed improvements in IIEF-15 assessment as well as increased vascularization of the corpora based on penile Doppler arterial velocity measurements. Although promising, further investigation in humans is required to substantiate BM-MNCs impact on erections, and erectile function recovery going forward.