TY - JOUR
T1 - Liver transplantation
T2 - New treatment for mucopolysaccharidosis type VI in rats
AU - Toyama, Sumika
AU - Migita, Ohsuke
AU - Fujino, Masayuki
AU - Kunieda, Tetsuo
AU - Kosuga, Motomichi
AU - Fukuhara, Yasuyuki
AU - Nagahara, Yukitoshi
AU - Li, Xiao Kang
AU - Okuyama, Torayuki
N1 - Funding Information:
The authors gratefully acknowledge Dr H. Kimura for his critical comments and useful suggestions. We thank Dr Bin Yu for invaluable technical support in the liver transplantation procedure. We also thank Emma Barber, an English-language editor at the National Center for Child Health and Development, for editing a version of this paper. This study was supported by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the National Center for Child Health and Development.
Publisher Copyright:
© 2018 Japan Pediatric Society
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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: 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: 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: 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.
AB - 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: 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: 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: 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.
KW - arylsulfatase B
KW - glycosaminoglycan
KW - liver transplantation
KW - lysosomal storage disorder
KW - mucopolysaccharidosis VI
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UR - http://www.scopus.com/inward/citedby.url?scp=85062061861&partnerID=8YFLogxK
U2 - 10.1111/ped.13751
DO - 10.1111/ped.13751
M3 - Article
C2 - 30548979
AN - SCOPUS:85062061861
VL - 61
SP - 180
EP - 189
JO - Pediatrics International
JF - Pediatrics International
SN - 1328-8067
IS - 2
ER -