Fiscal Year:
2007
Title:
Novel Intervention for Colitis
Agency:
HHS
Contract:
1R41DK075161-01A1
Award Amount:
$279,250.00
Abstract:
DESCRIPTION (provided by applicant): Novel Intervention for Colitis The scope of the current proposal is to determine whether administration of an apoE mimetic peptide, COG112, improves clinical, histological and inflammatory outcomes in clinically relevan
t paradigms of colitis. Specifically, we will employ the acute Citrobacter rodentium (C. rodentium) model, an acute Dextran Sulfate Sodium (DSS) model and a chronic DSS model of colitis. We will also define whether there is a dose-dependent response to tre
atment with COG112 in these models of human disease. This course of experiments has the potential to represent a novel therapeutic strategy for a difficult gastrointestinal disease in which adequate treatment strategies do not currently exist. Specific Aim
1: Using a C. rodentium-infectious model of acute colitis, measure the response to treatment with different doses of COG112 using clinical outcome measures, histological outcome measures and measures of a panel of representative inflammatory mediators. Sp
ecific Aim 2: Using a DSS model of acute colitis, measure the response to treatment with different doses of COG112 using clinical outcome measures, histological outcome measures and measures of a panel of representative inflammatory mediators. Specific Aim
3: Using a DSS model of chronic colitis, measure the response to treatment with different doses of COG112 using clinical outcome measures, histological outcome measures and measures of a panel of representative inflammatory mediators. Novel Intervention f
or Colitis: Inflammatory Bowel Disease (IBD), more commonly known as Crohn's disease and ulcerative colitis, affects approximately 1 million Americans with inflammation of the intestines, abdominal pain, cramping and diarrhea. These symptoms vary in severi
ty, but are often debilitating for patients to the extent that they greatly alter their quality of life. We have found that clinical and histological scores of IBD are less when the levels of small molecules known as polyamines are increased. To increase p
olyamine levels, one needs to increase the amount of arginine, an amino acid derived from our diets, that is converted to polyamines through the action of the arginase/ornithine decarboxylase pathway. We have found a novel drug, COG112, can stimulate this
arginase activity. Thus, mouse models of colitis treated with COG112 should have less disease than their untreated counterparts. So we propose to directly measure whether COG112 will exacerbate or ameliorate colitis in mouse models.
Small Business Information at Submission:
COGNOSCI, INC.
COGNOSCI, INC. 79 T. W. Alexander Drive RESEARCH TRIANGLE PARK, NC 27709
EIN/Tax ID:
562208520
DUNS:
N/A
Number of Employees:
N/A
Woman-Owned:
No
Minority-Owned:
No
HUBZone-Owned:
No
Research Institution Information:
VANDERBILT UNIVERSITY MEDICAL
VANDERBILT UNIVERSITY
Medical Center
NASHVILLE, TN 37203 6869
RI Type:
Nonprofit college or university