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Thermosenitive TRPM8 channels and diabetic erectile dysfunction
Summary Data Summary
Applicant Webb, Clinton
E-Mail Address cwebb@augusta.edu
Project Title Thermosenitive TRPM8 channels and diabetic erectile dysfunction
CBU ID 18AU3921
External SubContract ID 32307-72
Diabetic Complication Uropathy
Funding Program Group Pilot & Feasibility [PF2018]
Abstract Erectile dysfunction (ED) seriously diminishes quality of life and is a warning
of undetected circulatory problems elsewhere in the body. Diabetes increases the
risk of ED and the onset may be at a relatively young age. ED prevalence is
expected to increase due to rising diabetes rates from obesity, population
aging, and increased number of children diagnosed with type 2 diabetes. A wide
variety of therapeutic options are available for the treatment of ED, including
vacuum therapy, intra-cavernous and transurethral drug therapy, surgery and oral
medications. Unfortunately, despite these options, ED persists in many patients.
Viagra and other phosphodiesterase-5 (PDE5) inhibitors have been successful in
the treatment of many forms of ED, but often, patients fail to benefit from use
of these agents. This is particularly relevant to diabetic patients where it is
estimated that as many as 40-60% do not respond to PDE5 inhibitors. Also, PDE5
inhibitors are often contraindicated in diabetic patients because they take
nitrates for angina or myocardial infarction. Thus, there is a critical need to
develop alternative therapeutic agents to treat ED in diabetic patients.
Transient receptor potential (TRP) channels are typically Ca2+ permeable,
polymodal and display variable gating mechanisms. They are expressed in a wide
variety of cell types, where they are involved in many physiological functions.
Thus, dysfunction of these channels can cause important acquired or inherited
human diseases. The goal of this project is to investigate the role of
thermosensitive TRPM8 channels in the internal pudendal arteries and corpus
cavernosum, tissues that are critical for sexual function and known to undergo
pathological changes due to the diabetic state. This research plan will also
test the innovative hypothesis that in diabetes, a therapeutic approach
utilizing agonists at TRPM8 will improve the erection in diabetes. Three
specific aims are proposed: 1) to investigate the expression and mechanism of
action of TRPM8 activation in the pudendal artery and corpus cavernosum from
diabetic mice (db/db) and their nondiabetic controls; 2) to confirm the
mechanism of action of TRPM8 activation in db/db mice using a knockdown strategy
to reduce TRPM8 channel expression in tissues isolated form db/db mice and their
controls; 3) to test the hypothesis that chronic administration of a TRPM8
agonist (menthol and icilin, osmotic minipump) in diabetic leads to the
prevention and improvement of ED.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel Dr. R. Clinton Webb
Dr. Darizy Flávia Silva Amorim de Vasconcelos
Salary Total Costs 49813
Supply Total Costs 38096
Equipment Total Costs 0
Travel/Other Total Costs 3000
Direct Costs 90909
Indirect Costs Proposed 9091
Total Costs Proposed 100000
Total Costs Approved 39746
Start Date 1/1/2019
End Date 3/31/2021
IFO Name Vazquez, Diego
IFO E-Mail Address ogc@augusta.edu
IACUC/IRB No. 99999
IACUC/IRB Institution Augusta University
Entity ID No. 1-58-1418202-A1
Report Request Date 1/31/2021
T1D NO
TypeCount
Invoices 13
Progress Reports 2
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  18AU392132307-72Augusta University9/15/2021$401.32$40.13$441.45$51.06View PDF
  View  18AU392132307-72Augusta University8/15/2021$5,758.62$575.86$6,334.48$51.06View PDF
  View  18AU392132307-72Augusta University7/12/2021$3,740.45$341.66$4,082.11$51.06View PDF
  View  18AU392132307-72Augusta University6/7/2021$7,342.93$734.30$8,077.23$51.06View PDF
  View  18AU392132307-72Augusta University5/6/2021$3,841.66$384.18$4,225.84$51.06View PDF
  View  18AU392132307-72Augusta University3/31/2021$4,924.77$492.49$5,417.26$51.06View PDF
  View  18AU392132307-72Augusta University3/15/2021$1,865.27$186.54$2,051.81$51.06View PDF
  View  18AU392132307-72Augusta University2/9/2022$795.11$79.51$874.62$51.06View PDF
  View  18AU392132307-72Augusta University2/4/2021$1,865.26$186.54$2,051.80$51.06View PDF
  View  18AU392132307-72Augusta University12/4/2020$1,859.70$185.98$2,045.68$51.06View PDF
  View  18AU392132307-72Augusta University11/6/2020$1,402.65$140.27$1,542.92$51.06View PDF
  View  18AU392132307-72Augusta University11/5/2021$452.67$45.27$497.94$51.06View PDF
  View  18AU392132307-72Augusta University1/14/2021$1,865.26$186.54$2,051.80$51.06View PDF
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