title: Improvement in erectile dysfunction after neurotrophic factor gene therapy in diabetic rats.
abstract: OBJECTIVE
  Erectile dysfunction (ED) is a common but difficult to treat complication of diabetes mellitus (DM). We have previously reported herpes simplex virus (HSV) vector mediated delivery of nerve growth factor into the bladder to treat diabetic cystopathy and neurotrophin-3 (NT3) gene transfer for pyridoxine treatment. Nerve growth factor and NT3 are neurotrophic factors that may protect nerves from mechanical and metabolic damage. We investigated the effects of HSV mediated delivery of NT3 for the treatment of diabetic ED.
  
  
  METHODS
  Male Sprague-Dawley rats weighing 300 to 400 gm were injected with 65 mg/kg streptozotocin to induce DM. After 4 weeks 20 microl containing 5 x 10 pfu replication defective HSV vector expressing lacZ (6 rats) or NT3 (6) were injected directly into the cavernous nerve sheath with a 30 gauge needle. Four weeks later the animals underwent measurement of intracavernous pressure under electrical stimulation (20 Hz, 0.5 millisecond and 10 V) of the cavernous nerve. Staining for lacZ and neuronal nitric oxide synthase in the major pelvic ganglia was also performed.
  
  
  RESULTS
  beta-Galactosidase staining revealed lacZ positive neurons in the major pelvic ganglia. Maximal intracavernous pressure induced by electrical stimulation showed statistically significant mean values +/- SEM of 15.1 +/- 2.1 and 43.8 +/- 11.1 cm H2O in the lacZ and NT3 vector injected groups, respectively (p = 0.03). The mean number of neuronal nitric oxide synthase positive neurons per section in the NT3 group was significantly higher than that in the lacZ control group at 3.33 +/- 0.23 and 0.64 +/- 0.14 neurons per high power field, respectively (p < 0.001).
  
  
  CONCLUSIONS
  We report that gene therapy for the treatment of diabetic ED is feasible with HSV vectors. NT3 gene therapy may be applicable for the treatment of ED induced by DM.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Nelson E
authors.initials: NE
authors.lastname: Bennett
authors.forename: Jang H
authors.initials: JH
authors.lastname: Kim
authors.forename: Darren P
authors.initials: DP
authors.lastname: Wolfe
authors.forename: Katsumi
authors.initials: K
authors.lastname: Sasaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.forename: William F
authors.initials: WF
authors.lastname: Goins
authors.forename: Shaohua
authors.initials: S
authors.lastname: Huang
authors.forename: Joel B
authors.initials: JB
authors.lastname: Nelson
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Glorioso
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000628:therapy*; D007172:Erectile Dysfunction / Q000209:etiology* / Q000628:therapy*; D015316:Genetic Therapy; D008297:Male; D020933:Neurotrophin 3 / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus
chemical_list: D020933:Neurotrophin 3