Lysosomal storage diseases(LSDs) result from deficiencies of lysosomal enzymes leading to accumulation of precursor products. The stored material eventually leads to diffuse tissue disease and premature death. Mucopolysaccharidosis VII(MPS VII) is a representative LSD characterized by absent or severely decreased levels of B-glucuronidase, with both CNS and systemic involvement. Gene transfer strategies are being investigated as a therapy to provide for a long-lasting, endogenous source of beta-glucuronidase. Preliminary data obtained with recombinant adeno-associated viruses types 4 and 5(AAV4 and AAV5) reporter viruses suggest that AAV4 or AAV5 could efficiently mediate beta-glucuronidase gene transfer to brain. As such, we propose experiments to better understand these novel vectors and to investigate their ability to correct LSD in brain. These experiments are to answer the following questions:
SPECIFIC AIM 1 : Can AAV5-beta-glucuronidase correct lysosomal storage diseases in the CNS of the MPSVII mouse? SPECIFIC AIM 2: Is there a polarity to AAV4-mediated ependymal cell transduction? SPECIFIC AIM 3: Can the extent of gene transfer with AAV4 and AAV5 be increased by delivery through minipumps? SPECIFIC AIM 4: Can AAV4 and AAV5 transduce cells in human brain tissue?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HD008692-01
Application #
6208964
Study Section
Special Emphasis Panel (ZRG1-BIO (02))
Program Officer
Oster-Granite, Mary Lou
Project Start
2000-07-01
Project End
2001-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
1
Fiscal Year
2000
Total Cost
$39,232
Indirect Cost
Name
University of Iowa
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242