TY - JOUR
T1 - Enzyme replacement therapy from birth in a feline model of mucopolysaccharidosis type VI
AU - Crawley, Allison C.
AU - Niedzielski, Krystyna H.
AU - Isaac, Elizabeth L.
AU - Davey, Richard C.A.
AU - Byers, Sharon
AU - Hopwood, John J.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1997/2/15
Y1 - 1997/2/15
N2 - We report evidence of a dose responsive effect of enzyme replacement therapy in mucopolysaccharidosis type VI cats from birth, at the clinical, biochemical, and histopathological level. Cats treated with weekly, intravenous recombinant human N-acetylgalactosamine-4-sulfatase at 1 and 5 mg/kg, were heavier, more flexible, had greatly reduced or no spinal cord compression, and had almost normal urinary glycosaminoglycan levels. There was near normalization or complete reversal of lysosomal storage in heart valve, aorta, skin, dura, liver, and brain perivascular cells. No reduction in lysosomal vacuolation was observed in cartilage or cornea; however, articular cartilage was thinner and external ear pinnae were larger in some treated cats. Degenerative joint changes were not obviously delayed in treated cats. Skeletal pathology was reduced, with more normalized bone dimensions and with more uniform bone density and trabecular pattern clearly visible on radiographs by 5 to 6 mo; however, differences between 1 and 5 mg/kg dose rates were not clearly distinguishable. At a dose of 0.2 mg/kg, disease was not significantly altered in the majority of parameters examined. Lysosomal storage was present in all tissues examined in the midterm mucopolysaccharidosis type VI fetus and increased rapidly in extent and severity from birth.
AB - We report evidence of a dose responsive effect of enzyme replacement therapy in mucopolysaccharidosis type VI cats from birth, at the clinical, biochemical, and histopathological level. Cats treated with weekly, intravenous recombinant human N-acetylgalactosamine-4-sulfatase at 1 and 5 mg/kg, were heavier, more flexible, had greatly reduced or no spinal cord compression, and had almost normal urinary glycosaminoglycan levels. There was near normalization or complete reversal of lysosomal storage in heart valve, aorta, skin, dura, liver, and brain perivascular cells. No reduction in lysosomal vacuolation was observed in cartilage or cornea; however, articular cartilage was thinner and external ear pinnae were larger in some treated cats. Degenerative joint changes were not obviously delayed in treated cats. Skeletal pathology was reduced, with more normalized bone dimensions and with more uniform bone density and trabecular pattern clearly visible on radiographs by 5 to 6 mo; however, differences between 1 and 5 mg/kg dose rates were not clearly distinguishable. At a dose of 0.2 mg/kg, disease was not significantly altered in the majority of parameters examined. Lysosomal storage was present in all tissues examined in the midterm mucopolysaccharidosis type VI fetus and increased rapidly in extent and severity from birth.
KW - disease models, animal
KW - dysostoses
KW - genetics, medical
KW - lysosomal storage diseases
KW - mucopolysaccharidosis VI
UR - http://www.scopus.com/inward/record.url?scp=0031029536&partnerID=8YFLogxK
U2 - 10.1172/JCI119208
DO - 10.1172/JCI119208
M3 - Article
C2 - 9045867
AN - SCOPUS:0031029536
SN - 0021-9738
VL - 99
SP - 651
EP - 662
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 4
ER -