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Treatment of Diabetic Nephropathy through Modulation of Lipoprotein Metabolism
Summary Data Summary
Applicant Attie, Alan
E-Mail Address adattie@wisc.edu
Project Title Treatment of Diabetic Nephropathy through Modulation of Lipoprotein Metabolism
CBU ID 17AU3822
External SubContract ID 32307-10
Diabetic Complication Nephropathy
Funding Program Group Pilot & Feasibility [PF2017]
Abstract Genetic and environmental factors contribute to the risk of diabetic nephropathy
(DN) among people with diabetes. Inflammation is a key feature of DN.
Inflammation is likewise a key feature of atherosclerosis. Hyperlipidemia plays
a key causal role in atherosclerosis and its relationship to the inflammatory
processes is quite well-studied. However, the role of hyperlipidemia in DN is
less well explored. However, there is evidence linking hypertriglyceridemia with
DN. A mechanism that links hyperlipidemia with atherosclerosis is the production
of adducts between proteins and oxidized lipids. These adducts are epitopes that
are recognized by the innate and adaptive immune responses and initiate an
inflammatory process. We present evidence that oxidation epitopes present in
human atherosclerosis are also present in DN. Thus, the premise of this proposal
is that there is a common etiology between the inflammatory processes that
underlie atherosclerosis and diabetic nephropathy. Ionis, Inc. has developed
antisense oligonucleotides (ASOs) against apoC3, for the treatment of
hypertriglyceridemia. Reducing apoC3 levels increases lipoprotein
lipase-mediated removal of triglycerides from the bloodstream, primarily in
adipose tissue. The anti-apoC3 ASOs are safe and effective, and currently in use
in the clinic. The two principal investigators of this P&F proposal, Alan Attie
and Charles Alpers, identified the BTBR-ob/ob mouse as an excellent model of
human DN. The objective of this P&F project is to test the hypothesis that
targeted ASO therapy for the dyslipidemia characteristic both of the BTBR-ob/ob
mouse and humans with T2D will prevent the development of DN. The project will
develop a treatment protocol using Ionis ASOs to normalize triglycerides in
BTBR-ob/ob mice. Animals will then be treated and their nephropathy analyzed by
measurement of urinary albumin, total protein, and urea. Kidneys will be
analyzed histologically and by electron microscopy. The kidneys will be probed
for the expression of lipid oxidation protein epitopes similar to those seen in
atherosclerotic lesions. The studies will determine whether diversion of plasma
lipids to adipose tissue will spare kidneys of nephropathy in the setting of
type 2 diabetes.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel Charles Alpers; Donald Stapleton; Kathryn Schueler
Salary Total Costs 30747
Supply Total Costs 13765
Equipment Total Costs 0
Travel/Other Total Costs 24664
Direct Costs 69176
Indirect Costs Proposed 30824
Total Costs Proposed 100000
Total Costs Approved 100000
Start Date 11/1/2017
End Date 10/31/2018
IFO Name Marcotte, Sarah
IFO E-Mail Address sarah.marcotte@wisc.edu
IACUC/IRB No. A3368-01
IACUC/IRB Institution University of Wisconsin-Madison
Entity ID No. 396006492
Report Request Date 11/30/2018
T1D NO
TypeCount
Invoices 10
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  17AU382232307-10University of Wisconsin-Madison9/5/2018$7,385.43$3,914.22$11,299.65$4,778.45View PDF
  View  17AU382232307-10University of Wisconsin-Madison8/2/2018$1,400.52$742.28$2,142.80$4,778.45View PDF
  View  17AU382232307-10University of Wisconsin-Madison7/3/2018$7,593.03$4,024.31$11,617.34$4,778.45View PDF
  View  17AU382232307-10University of Wisconsin-Madison6/4/2018$14,941.87$7,919.18$22,861.05$4,778.45View PDF
  View  17AU382232307-10University of Wisconsin-Madison5/2/2018$7,418.97$3,931.96$11,350.93$4,778.45View PDF
  View  17AU382232307-10University of Wisconsin-Madison4/3/2018$1,648.03$873.45$2,521.48$4,778.45View PDF
  View  17AU382232307-10University of Wisconsin-Madison3/2/2018$1,332.38$706.16$2,038.54$4,778.45View PDF
  View  17AU382232307-10University of Wisconsin-Madison2/2/2018$1,332.38$706.16$2,038.54$4,778.45View PDF
  View  17AU382232307-10University of Wisconsin-Madison12/28/2018$15,000.71$4,175.89$19,176.60$4,778.45View PDF
  View  17AU382232307-10University of Wisconsin-Madison10/2/2018$6,176.13$3,998.49$10,174.62$4,778.45View PDF


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