Comparative study of idursulfase beta and idursulfase in vitro and in vivo.
Hunter syndrome is an X-linked lysosomal storage disease caused by a deficiency in the enzyme iduronate-2-sulfatase (IDS), leading to the accumulation of glycosaminoglycans (GAGs). Two recombinant enzymes, idursulfase and idursulfase beta are currently available for enzyme replacement therapy for Hunter syndrome. These two enzymes exhibited some differences in various clinical parameters in a recent clinical trial. Regarding the similarities and differences of these enzymes, previous research has characterized their biochemical and physicochemical properties. We compared the in vitro and in vivo efficacy of the two enzymes on patient fibroblasts and mouse model. Two enzymes were taken up into the cell and degraded GAGs accumulated in fibroblasts. In vivo studies of two enzymes revealed similar organ distribution and decreased urinary GAGs excretion. Especially, idursulfase beta exhibited enhanced in vitro efficacy for the lower concentration of treatment, in vivo efficacy in the degradation of tissue GAGs and improvement of bones, and revealed lower anti-drug antibody formation. A biochemical analysis showed that both enzymes show largely a similar glycosylation pattern, but the several peaks were different and quantity of aggregates of idursulfase beta was lower.
Protein Engineering Laboratory, MOGAM Institute for Biomedical Research, Yongin, Republic of Korea.
Chihwa
C
Kim
Research Center, Green Cross Corporation, Yongin, Republic of Korea.
Jinwook
J
Seo
Research Center, Green Cross Corporation, Yongin, Republic of Korea.
Yokyung
Y
Chung
Corporate Development, Green Cross Corporation, Yongin, Republic of Korea.
Hyi-Jeong
HJ
Ji
Research Center, Green Cross Corporation, Yongin, Republic of Korea.
Jaehyeon
J
Lee
Research Center, Green Cross Corporation, Yongin, Republic of Korea.
Jongmun
J
Sohn
Research Center, Green Cross Corporation, Yongin, Republic of Korea.
Byoungju
B
Lee
Protein Engineering Laboratory, MOGAM Institute for Biomedical Research, Yongin, Republic of Korea.
Eui-Cheol
EC
Jo
D000818:Animals; D002460:Cell Line; D056947:Enzyme Replacement Therapy / Q000379:methods*; D006023:Glycoproteins / Q000235:genetics; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007066:Iduronate Sulfatase / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016532:Mucopolysaccharidosis II / Q000188:drug therapy* / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D006023:Glycoproteins; D006025:Glycosaminoglycans; C018322:IDS protein, human; D007066:Iduronate Sulfatase; C517982:idursulfase; C000619301:idursulfase beta, mouse