Abstract

The overall goal of this proposal is to test the efficacy of a novel mechanism to prevent or delay diabetic complications (DC) by enhancing the removal and clearance of toxic glucose metabolites. The objective of this project is to evaluate the effect of over-expression of mouse LZ (mLZ), a non-toxic native peptide, by adenovirus vector based gene transfer in diabetic nude mice in enhancing the removal of AGEs, thus aborting their toxic impact on multiple tissues, herein focusing on the kidney.
The specific aims i nclude:
Aim 1 A. In vivo characterization of mLZ-expressing E1-deleted adenovirus vector (Ad.E1-mLZ), and the determination of the efficacy of hepatoma cells to synthesize and secrete LZ;
Aim 1 B. Assessment of in vitro anti-AGE activity of mLZ and cellular processing of the mLZ:AGE complex;
Aim 2. In vivo testing of optimal gene transfer dosage, secretion and efficacy of mLZ against AGE accumulation and cellular toxicity;
and Aim 3. Investigation of the in vivo fate of mLZ:AGE complex and/or potential toxicity in nu/nuSTZ-diabetic mice.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DK057126-01
Application #
6053448
Study Section
Special Emphasis Panel (ZRG1-END (01))
Program Officer
Kimmel, Paul,
Project Start
1999-09-30
Project End
2001-08-31
Budget Start
1999-09-30
Budget End
2000-08-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Other Health Professions
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029