Articles

Smooth-Muscle–Specific Gene Transfer with the Human Maxi-K Channel Improves Erectile Function and Enhances Sexual Behavior in Atherosclerotic Cynomolgus Monkeys

By: George J. Christa lowast , Karl-Erik Anderssona, Koudy Williamsb, Weixin Zhaoa, Ralph D’Agostino Jr.c, Jay Kaplanb, Tamer Aboushwareba, James Yooa, Giulia Calendad, Kelvin P. Daviesd, Rani S. Sellerse and Arnold Melmand

Published online: 01 December 2009

Keywords: Gene therapy, Non-human primates, Erectile dysfunction, Gene transfer

Abstract Full Text Full Text PDF (1,7 MB)

Abstract

Background

Despite the advent of effective oral therapies for erectile dysfunction (ED), many patients are not successfully treated, and side effects have been documented.

Objective

To further evaluate the potential utility of naked DNA-based gene transfer as an attractive treatment option for ED.

Design, setting and participants

The effects of gene transfer on erectile function and sexual behavior were evaluated in eight male cynomolgus monkeys with ED secondary to moderately severe, diet-induced atherosclerosis.

Intervention

Following establishment of baseline characteristics, animals were subjected to intracavernous injection of a smooth-muscle–specific gene transfer vector (pSMAA-hSlo) encoding the pore-forming subunit of the human large-conductance, calcium-sensitive potassium channel (Maxi-K).

Measurements

For the sexual behavior studies, 2 wk of baseline data were obtained, and then animals were placed in the presence of estrogen-implanted females (n=2) three times per week for 30min, and sexual behavior was recorded. The intracavernous pressure response to papaverine injection was also monitored.

Results and limitations

Dramatic changes in erectile function and sexual behavior were observed after intracorporal gene transfer. The frequency of partial (6±2 to 10±2) and full (2±1.5 to 5±1.4) erections were significantly increased, with a parallel 2–3-fold increase in the duration of the observed erections. The frequency and latency of ejaculation were increased and decreased, respectively. Frequency and duration of grooming by the female were increased, and the latency decreased. Increased latency and decreased frequency of body contact was also observed, and this is characteristic of the typical drop in consort intimacy that occurs after mating in most macaque species. In addition, an increased responsiveness to intracavernous papaverine injection was observed.

Conclusions

The data indicate that intracorporal Maxi-K–channel gene transfer enhances erectile capacity and sexual behavior; the data imply that increased erectile function per se may lead to increased sexual function.

Take Home Message

Smooth-muscle–specific gene transfer has been shown to be an attractive therapeutic approach for the amelioration of age- and disease-related impairments in erectile function in two species. This study shows that gene-transfer–related enhancements in erectile function may lead to enhanced sexual behavior and function. These findings have important implications for the improved understanding and treatment of erectile dysfunction.

Keywords: Gene therapy, Non-human primates, Erectile dysfunction, Gene transfer.

Footnotes

a Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston Salem, NC, USA

b Wake Forest University Primate Center, Department of Comparative Medicine, Wake Forest University Health Sciences, Winston Salem, NC, USA

c Department of Public Health Sciences, Wake Forest University Health Sciences, Winston Salem, NC, USA

d Department of Urology, Albert Einstein College of Medicine, Bronx, NY, USA

e Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA

lowast Corresponding author. Wake Forest Institute for Regenerative Medicine, Wake Forest University Baptist Medical Center, BRF1, Room 442, Medical Center Blvd, Winston-Salem, NC 27157, USA. Tel. +1 336 713 7296; Fax: +1 336 713 7290.