Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 180-189 |
| Number of pages | 10 |
| Journal | Pediatrics International |
| Volume | 61 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2019 |
Fingerprint
Keywords
- arylsulfatase B
- glycosaminoglycan
- liver transplantation
- lysosomal storage disorder
- mucopolysaccharidosis VI
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
Cite this
Liver transplantation : New treatment for mucopolysaccharidosis type VI in rats. / Toyama, Sumika; Migita, Ohsuke; Fujino, Masayuki; Kunieda, Tetsuo; Kosuga, Motomichi; Fukuhara, Yasuyuki; Nagahara, Yukitoshi; Li, Xiao Kang; Okuyama, Torayuki.
In: Pediatrics International, Vol. 61, No. 2, 01.02.2019, p. 180-189.Research output: Contribution to journal › Article
}
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
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
UR - http://www.scopus.com/inward/record.url?scp=85062061861&partnerID=8YFLogxK
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 -