title: Smooth-muscle-specific gene transfer with the human maxi-k channel improves erectile function and enhances sexual behavior in atherosclerotic cynomolgus monkeys.
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.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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 30 min, and sexual behavior was recorded. The intracavernous pressure response to papaverine injection was also monitored.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University Primate Center, Department of Comparative Medicine, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA. gchrist@wfubmc.edu
authors.forename: George J
authors.initials: GJ
authors.lastname: Christ
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.forename: Koudy
authors.initials: K
authors.lastname: Williams
authors.forename: Weixin
authors.initials: W
authors.lastname: Zhao
authors.forename: Ralph
authors.initials: R
authors.lastname: D'Agostino
authors.forename: Jay
authors.initials: J
authors.lastname: Kaplan
authors.forename: Tamer
authors.initials: T
authors.lastname: Aboushwareb
authors.forename: James
authors.initials: J
authors.lastname: Yoo
authors.forename: Giulia
authors.initials: G
authors.lastname: Calenda
authors.forename: Kelvin P
authors.initials: KP
authors.lastname: Davies
authors.forename: Rani S
authors.initials: RS
authors.lastname: Sellers
authors.forename: Arnold
authors.initials: A
authors.lastname: Melman
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000150:complications* / Q000473:pathology; D007172:Erectile Dysfunction / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics*; D008252:Macaca fascicularis; D008297:Male; D009130:Muscle, Smooth / Q000502:physiology*; D010410:Penile Erection; D020127:Recovery of Function; D012726:Sexual Behavior, Animal
chemical_list: C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits