SPACE PROVIDED. Therapies for prostate cancer including radical surgery, radiation, hormonal therapy are the leading cause of iatrogenic erectile dysfunction (ED). The cavernous nerve, the nerve that controls penile erection, is on the capsule of the prostate and is frequently injured during radical pelvic surgery for cancer of the prostate as well as bladder and rectum. Supported by NIH grant "Treatment and prevention of impotence" RO 1 DK45370, Jan 1/1998- 12/31/2001, we found that systemic growth hormone and insulin-like growth factor (IGF) enhanced regeneration of the cavernous nerves and recovery of erectile function. However, the recovery is partial in young rats and minimal in old rats. In addition, concerns have been expressed regarding using growth hormone or IGF in patients after cancer therapy. Therefore, we performed several preliminary studies on the effect of neurotrophin on cavernous nerve regeneration and obtained very exciting results. The goals of this proposed project are to explore the potential of vascular endothelial growth factor (VEGF) - enhanced brain derived neurotrophic factor (BDNF) therapy on cavernous nerve regeneration and recovery of erectile function. In addition, we have identified that among the signaling pathways, Jak/STAT pathway seems to be the main one associated with BDNF enhanced neurite growth. We therefore also propose to confirm this finding and identify the missing link between BDNF and Jak/STAT pathway. We will also study the phosphorylation cascades, cytokine and growth factor expression associated with cavernous nerve injury and BDNF-enhanced regeneration. This proposal is aiming at improving our understanding of the molecular mechanism of cavernous nerve injury and regeneration and translate the knowledge to clinical use. Successful completion of this project will not only significantly improve our understanding of the basic mechanism of cavernous nerve injury and regeneration but may also offer a "cure" for neurogenic ED from various causes to tens of thousands of patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK045370-15
Application #
8208199
Study Section
Special Emphasis Panel (ZRG1-UROL (01))
Program Officer
Rankin, Tracy L
Project Start
1994-08-01
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
15
Fiscal Year
2012
Total Cost
$363,727
Indirect Cost
$128,305
Name
University of California San Francisco
Department
Urology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Qiu, Xuefeng; Villalta, Jacqueline; Ferretti, Ludovic et al. (2012) Effects of intravenous injection of adipose-derived stem cells in a rat model of radiation therapy-induced erectile dysfunction. J Sex Med 9:1834-41
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