Gene Therapy for Neurogenic Erectile Dysfunction

被引:1
作者
Kato, Ryuichi [1 ,2 ]
Bennett, Nelson E. [1 ]
Kim, Jang Hang [1 ]
Wolfe, Darren [3 ]
Coyle, Christian H. [1 ]
Huang, Shaohua [4 ]
Wechuck, James B. [3 ]
Goins, William F. [4 ]
De Miguel, Fernando [1 ]
Tsukamoto, Taiji [2 ]
Nelson, Joel B. [1 ]
Glorioso, Joseph C. [4 ]
Chancellor, Michael B. [1 ]
Yoshimura, Naoki [1 ]
机构
[1] Univ Pittsburgh Sch Med, Dept Urol, Pittsburgh, PA 15213 USA
[2] Sapporo Med Univ Sch Med, Dept Urol, Sapporo, Hokkaido, Japan
[3] Diamyd Inc, Pittsburgh, PA USA
[4] Univ Pittsburgh Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA
关键词
cavernous nerve; diabetes mellitus; erectile dysfunction; gene therapy; herpes simplex virus;
D O I
10.1111/j.1757-5672.2009.00045.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Neurogenic erectile dysfunction (ED) is one of major causes of ED and is often difficult to treat. In this review, we report significant improvements of ED caused by diabetes mellitus (DM) or cavernous nerve injury by using a gene therapy approach in rat models of ED. Herpes simplex virus (HSV) vectors were used to deliver neurotrophic factors, such as neurotrophin 3 (NT3), glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN), into cavernous nerves. The retrograde transport of HSV vector-mediated neurotrophic factors to pelvic ganglion neurons occurred after the administration of the vector around the cavernous nerves. HSV vector administration around the cavernous nerves can improve DM-induced ED and promote the recovery of erectile function after cavernous nerve injury. The HSV vector-mediated delivery of neurotrophic factors could be applicable for the treatment of neurogenic ED. NT3, GDNF, and NTN would be the possible factors that could be used for this gene therapy application.
引用
收藏
页码:S44 / S47
页数:4
相关论文
共 14 条
[1]   ERECTILE DYSFUNCTION IN DIABETIC MEN - THE NEUROLOGICAL FACTOR REVISITED [J].
BEMELMANS, BLH ;
MEULEMAN, EJH ;
DOESBURG, WH ;
NOTERMANS, SLH ;
DEBRUYNE, FMJ .
JOURNAL OF UROLOGY, 1994, 151 (04) :884-889
[2]  
Bivalacqua Trinity J., 2004, V279, P173
[3]   Intracorporal injection of hSlo cDNA restores erectile capacity in STZ-diabetic F-344 rats in vivo [J].
Christ, GJ ;
Day, N ;
Santizo, C ;
Sato, YS ;
Zhao, WX ;
Sclafani, T ;
Bakal, R ;
Salman, M ;
Davies, K ;
Melman, A .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2004, 287 (04) :H1544-H1553
[4]   Differential gene expression of growth factors in young and old rat penile tissues is associated with erectile dysfunction [J].
Dahiya, R ;
Chui, R ;
Perinchery, G ;
Nakajima, K ;
Oh, BR ;
Lue, TF .
INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH, 1999, 11 (04) :201-206
[5]   Herpes simplex virus mediated nerve growth factor expression in bladder and afferent neurons: Potential treatment for diabetic bladder dysfunction [J].
Goins, WF ;
Yoshimura, N ;
Phelan, MW ;
Yokoyama, T ;
Fraser, MO ;
Ozawa, H ;
Bennett, N ;
de Groat, WC ;
Glorioso, JC ;
Chancellor, MB .
JOURNAL OF UROLOGY, 2001, 165 (05) :1748-1754
[6]   Glial cell line-derived neurotrophic factor is expressed in penis of adult rat and retrogradely transported in penile parasympathetic and sensory nerves [J].
Laurikainen, A ;
Hiltunen, JO ;
Vanhatalo, S ;
Klinge, E ;
Saarma, M .
CELL AND TISSUE RESEARCH, 2000, 302 (03) :321-329
[7]   Neurotrophic effects of vascular endothelial growth factor and neurotrophins on cultured major pelvic ganglia [J].
Lin, G ;
Chen, KC ;
Hsieh, PS ;
Yeh, CH ;
Lue, TF ;
Lin, CS .
BJU INTERNATIONAL, 2003, 92 (06) :631-635
[8]   Gene therapy of erectile dysfunction in the rat with penile neuronal nitric oxide synthase (vol 67, pg 20, 2002) [J].
Magee, TR ;
Ferrini, M ;
Garban, HJ ;
Vernet, D ;
Mitani, K ;
Rajfer, J ;
Gonzalez-Cadavid, F .
BIOLOGY OF REPRODUCTION, 2002, 67 (03) :1032-1041
[9]   The epidemiology and pathophysiology of erectile dysfunction [J].
Melman, A ;
Gingell, JC .
JOURNAL OF UROLOGY, 1999, 161 (01) :5-11
[10]   The first human trial for gene transfer therapy for the treatment of erectile dysfunction: Preliminary results [J].
Melman, A ;
Bar-Chama, N ;
McCullough, A ;
Davies, K ;
Christ, G .
EUROPEAN UROLOGY, 2005, 48 (02) :314-318