We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Long-term expression and transfer of arylsulfatase A into brain of arylsulfatase A-deficient mice transplanted with bone marrow expressing the arylsulfatase A cDNA from a retroviral vector.
- Authors
Matzner, U; Harzer, K; Learish, R D; Barranger, J A; Gieselmann, V
- Abstract
A deficiency of arylsulfatase A (ASA) results in the lysosomal lipid storage disease metachromatic leukodystrophy. The disease mainly affects the central nervous system causing a progressive demyelination. A therapeutic effect will depend on the delivery of the deficient enzyme to the central nervous system. We have transplanted ASA-deficient mice with bone marrow transduced with a retroviral vector expressing the human ASA cDNA. Aft transplanted animals initially showed high serum levels of human ASA. In 50% of the recipients high ASA serum levels were sustained for 12 months after transplantation. In the remaining mice, serum levels decreased rapidly to low or undetectable levels. ASA activity and immunoreactivity was detectable in aft organs of animals with continuous levels of ASA in serum. Most notably, substantial amounts of ASA activity were transferred into the brain, reaching up to 33% of the normal tissue level. In contrast to peripheral organs, the amount of enzyme delivered to the brain did not correlate with ASA serum levels as an indicator of overexpression. This reveals that enzyme transfer to the brain is not due to endocytosis of serum ASA by endothelial cells, but rather to bone marrow derived cells migrated into the brain.
- Subjects
ARYLSULFATASES; BONE marrow; RETROVIRUSES; GENETIC transformation
- Publication
Gene Therapy, 2000, Vol 7, Issue 14, p1250
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301232