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Testing of a selective integrin inhibitor in a type 1 model of diabetic nephropathy
Summary Data Summary
Applicant Pozzi, Ambra
E-Mail Address ambra.pozzi@vanderbilt.edu
Project Title Testing of a selective integrin inhibitor in a type 1 model of diabetic
nephropathy
CBU ID 14GHSU1465
External SubContract ID 25034-60
Diabetic Complication Nephropathy
Funding Program Group Pilot & Feasibility [PF2015] Preclinical
Abstract Chronic Kidney Disease (CKD) affects over 20 million people in the US with
treatment of US individuals having end-stage renal disease (ESRD) costing
Medicare over $32 billion in 2010. The most frequent causes of ESRD are
hypertension and diabetes. Despite treatment of CKD with reno-protective agents,
many individuals, particularly those with type 1 diabetes, progress to ESRD.
Thus, there is urgent need for an effective treatment for CKD. Irrespective of
the cause of CKD, fibrosis is a key underlying feature and plays a major role in
progression to ESRD. Fibrosis is characterized by the abnormal deposition of
extracellular matrix components including collagen within the glomeruli and
along the tubules of the kidneys. The regulation of matrix components depends on
many factors, including cell-matrix interactions via integrins. Integrins are
transmembrane receptors consisting of an a and ß subunit non-covalently bound.
Upon ligand binding, they activate intracellular signaling pathways to control
various functions including matrix synthesis/degradation. The integrin we focus
on is a collagen receptor and contributes to kidney fibrosis by positively
regulating collagen production. In support of this finding, genetic and
pharmacological inhibition of this receptor in mice ameliorates kidney fibrosis
following adriamycin-mediated injury. These data suggest that inhibition of this
receptor might be beneficial in the setting of fibrotic diseases, including
diabetic nephropathy (DN). Inhibitors of the integrin of interest have only been
used in prevention studies, as treatment was started at the time of kidney
injury. The goal of this grant is to evaluate the efficacy of a small-molecule
inhibitor of the integrin of interest to slow and ideally halt the progression
to diabetes-mediated nephropathy in a mouse model of type 1 diabetes. Positive
proof-of-concept will be assessed by reductions in albuminuria, glomerular and
interstitial fibrosis, glomerular basement thickening, and improvement of
glomerular filtration rate. This study will provide the first preclinical
proof-of-concept for inhibitors of this integrin to be efficacious in DN.
Positive results will initiate funding proposals for identification and testing
of novel inhibitors of this integrin, with properties suitable for clinical
development, in preclinical models of DN.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 17457
Supply Total Costs 20759
Equipment Total Costs 0
Travel/Other Total Costs 0
Direct Costs 38216
Indirect Costs Proposed 21784
Total Costs Proposed 60000
Total Costs Approved 60000
Start Date 10/1/2015
End Date 10/31/2016
IFO Name Thomson, Angela
IFO E-Mail Address angela.thomson@vanderbilt.edu
IACUC/IRB No. 99999
IACUC/IRB Institution Vanderbilt University
Entity ID No.
Report Request Date 10/31/2016
T1D NO
TypeCount
Invoices 9
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  14GHSU146525034-60Vanderbilt University8/5/2016$5,660.14$3,226.28$8,886.42$710.24View PDF
  View  14GHSU146525034-60Vanderbilt University7/19/2016$4,251.92$2,423.59$6,675.51$710.24View PDF
  View  14GHSU146525034-60Vanderbilt University6/8/2016$4,279.31$2,439.21$6,718.52$710.24View PDF
  View  14GHSU146525034-60Vanderbilt University5/18/2016$4,988.97$2,843.71$7,832.68$710.24View PDF
  View  14GHSU146525034-60Vanderbilt University4/8/2016$3,768.86$2,148.25$5,917.11$710.24View PDF
  View  14GHSU146525034-60Vanderbilt University3/7/2016$3,686.41$2,101.25$5,787.66$710.24View PDF
  View  14GHSU146525034-60Vanderbilt University2/5/2016$4,953.11-$4,953.11$710.24View PDF
  View  14GHSU146525034-60Vanderbilt University12/15/2016$2,473.72$1,410.03$3,883.75$710.24View PDF
  View  14GHSU146525034-60Vanderbilt University1/11/2016$8,635.00-$8,635.00$710.24View PDF


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