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Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: early treatment rescues bone lesions?
- Source :
-
Molecular genetics and metabolism [Mol Genet Metab] 2015 Feb; Vol. 114 (2), pp. 195-202. Date of Electronic Publication: 2014 Jun 04. - Publication Year :
- 2015
-
Abstract
- We treated mucopolysaccharidosis IVA (MPS IVA) mice to assess the effects of long-term enzyme replacement therapy (ERT) initiated at birth, since adult mice treated by ERT showed little improvement in bone pathology [1]. To conduct ERT in newborn mice, we used recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in a CHO cell line. First, to observe the tissue distribution pattern, a dose of 250units/g body weight was administered intravenously in MPS IVA mice at day 2 or 3. The infused enzyme was primarily recovered in the liver and spleen, with detectable activity in the bone and brain. Second, newborn ERT was conducted after a tissue distribution study. The first injection of newborn ERT was performed intravenously, the second to fourth weekly injections were intraperitoneal, and the remaining injections from 5th to 14th weeks were intravenous into the tail vein. MPS IVA mice treated with GALNS showed clearance of lysosomal storage in the liver and spleen, and sinus lining cells in bone marrow. The column structure of the growth plate was organized better than that in adult mice treated with ERT; however, hyaline and fibrous cartilage cells in the femur, spine, ligaments, discs, synovium, and periosteum still had storage materials to some extent. Heart valves were refractory to the treatment. Levels of serum keratan sulfate were kept normal in newborn ERT mice. In conclusion, the enzyme, which enters the cartilage before the cartilage cell layer becomes mature, prevents disorganization of column structure. Early treatment from birth leads to partial remission of bone pathology in MPS IVA mice.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Administration, Intravenous
Animals
Animals, Newborn
Bone Diseases pathology
CHO Cells
Cartilage drug effects
Cartilage ultrastructure
Chondrocytes drug effects
Chondrocytes ultrastructure
Chondroitinsulfatases administration & dosage
Chondroitinsulfatases genetics
Chondroitinsulfatases pharmacokinetics
Cricetulus
Disease Models, Animal
Growth Plate drug effects
Growth Plate ultrastructure
Keratan Sulfate blood
Liver drug effects
Mice
Mice, Knockout
Mucopolysaccharidosis IV pathology
Recombinant Proteins administration & dosage
Recombinant Proteins pharmacokinetics
Recombinant Proteins therapeutic use
Spleen drug effects
Tissue Distribution drug effects
Bone Diseases drug therapy
Chondroitinsulfatases therapeutic use
Enzyme Replacement Therapy
Mucopolysaccharidosis IV drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1096-7206
- Volume :
- 114
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular genetics and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 24953405
- Full Text :
- https://doi.org/10.1016/j.ymgme.2014.05.013