Liver transplantation: New treatment for mucopolysaccharidosis type VI in rats.
arylsulfatase B
glycosaminoglycan
liver transplantation
lysosomal storage disorder
mucopolysaccharidosis VI
Journal
Pediatrics international : official journal of the Japan Pediatric Society
ISSN: 1442-200X
Titre abrégé: Pediatr Int
Pays: Australia
ID NLM: 100886002
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
received:
13
04
2018
revised:
22
08
2018
accepted:
26
10
2018
pubmed:
15
12
2018
medline:
12
3
2019
entrez:
15
12
2018
Statut:
ppublish
Résumé
Mucopolysaccharidosis (MPS) VI is a rare, autosomal recessive congenital metabolic disorder caused by deficient activity of the lysosomal metabolic enzyme, N-acetylgalactosamine 4-sulfatase. Enzyme replacement therapy (ERT) is the current treatment for MPS VI, although it involves limited compliance to the therapy and high cost. The aim of this study was to develop a new method of treatment by conducting an orthotopic liver transplantation (LTx) using an animal model of human MPS VI, and to evaluate and examine its effectiveness for treating MPS VI. LTx was carried out from normal unaffected to affected MPS VI rats (MPR), which were then killed after LTx, and tissues from the heart, spleen, and knee joint, as well as serum, collected for biological and morphologic evaluation. Liver-transplanted (LTx) MPR had the same level of N-acetylgalactosamine 4-sulfatase activity in the liver and lungs as normal unaffected MPR, and the urinary secretion of mucopolysaccharides/glycosaminoglycan (GAG) in LTx MPR was significantly decreased. Furthermore, on histopathology, the spleens of LTx MPR showed elimination of vacuole cells. In the knee joints, growth plates became thinner, and on radiography the facial and cranial bones of LTx MPR were morphologically normal. LTx from normal to affected MPR was effective for symptoms of MPS and accumulation of GAG, suggesting that LTx could be a promising alternative approach for MPS VI.
Sections du résumé
BACKGROUND
BACKGROUND
Mucopolysaccharidosis (MPS) VI is a rare, autosomal recessive congenital metabolic disorder caused by deficient activity of the lysosomal metabolic enzyme, N-acetylgalactosamine 4-sulfatase. Enzyme replacement therapy (ERT) is the current treatment for MPS VI, although it involves limited compliance to the therapy and high cost. The aim of this study was to develop a new method of treatment by conducting an orthotopic liver transplantation (LTx) using an animal model of human MPS VI, and to evaluate and examine its effectiveness for treating MPS VI.
METHODS
METHODS
LTx was carried out from normal unaffected to affected MPS VI rats (MPR), which were then killed after LTx, and tissues from the heart, spleen, and knee joint, as well as serum, collected for biological and morphologic evaluation.
RESULTS
RESULTS
Liver-transplanted (LTx) MPR had the same level of N-acetylgalactosamine 4-sulfatase activity in the liver and lungs as normal unaffected MPR, and the urinary secretion of mucopolysaccharides/glycosaminoglycan (GAG) in LTx MPR was significantly decreased. Furthermore, on histopathology, the spleens of LTx MPR showed elimination of vacuole cells. In the knee joints, growth plates became thinner, and on radiography the facial and cranial bones of LTx MPR were morphologically normal.
CONCLUSIONS
CONCLUSIONS
LTx from normal to affected MPR was effective for symptoms of MPS and accumulation of GAG, suggesting that LTx could be a promising alternative approach for MPS VI.
Types de publication
Evaluation Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
180-189Subventions
Organisme : Ministry of Education, Culture, Sports, Science and Technology of Japan
Organisme : National Center for Child Health and Development
Informations de copyright
© 2018 Japan Pediatric Society.