A biochemical and physicochemical comparison of two recombinant enzymes used for enzyme replacement therapies of hunter syndrome.
Mucopolysaccharidosis II (MPS II, Hunter syndrome; OMIM 309900) is an X-linked lysosomal storage disease caused by a deficiency in the enzyme iduronate-2-sulfatase (IDS), leading to accumulation of glycosaminoglycans (GAGs). For enzyme replacement therapy (ERT) of Hunter syndrome, two recombinant enzymes, idursulfase (Elaprase(®), Shire Human Genetic Therapies, Lexington, MA) and idursulfase beta (Hunterase(®), Green Cross Corporation, Yongin, Korea), are currently available in Korea. To compare the biochemical and physicochemical differences between idursulfase and idursulfase beta, we examined the formylglycine (FGly) content, specific enzyme activity, mannose-6-phosphate (M6P) content, sialic acid content, and in vitro cell uptake activity of normal human fibroblasts of these two enzymes.The FGly content, which determines the enzyme activity, of idursulfase beta was significantly higher than that of idursulfase (79.4 ± 0.9 vs. 68.1 ± 2.2 %, P < 0.001). In accordance with the FGly content, the specific enzyme activity of idursulfase beta was significantly higher than that of idursulfase (42.6 ± 1.1 vs. 27.8 ± 0.9 nmol/min/μg protein, P < 0.001). The levels of M6P and sialic acid were not significantly different (2.4 ± 0.1 vs 2.4 ± 0.3 mol/mol protein for M6P and 12.3 ± 0.7 vs. 12.4 ± 0.4 mol/mol protein for sialic acid). However, the cellular uptake activity of the normal human fibroblasts in vitro showed a significant difference (Kuptake, 5.09 ± 0.96 vs. 6.50 ± 1.28 nM protein, P = 0.017).In conclusion, idursulfase beta exhibited significantly higher specific enzyme activity than idursulfase, resulting from higher FGly content. These biochemical differences may be partly attributed to clinical efficacy. However, long-term clinical evaluations of Hunter syndrome patients treated with these two enzymes will be needed to demonstrate the clinical implications of significant difference of the enzyme activity and the FGly content.
Department of Molecular Science and Technology, Ajou University, Suwon, South Korea.
Yo Kyung
YK
Chung
Young Bae
YB
Sohn
Jong Mun
JM
Sohn
Jieun
J
Lee
Mi Sun
MS
Chang
Younghee
Y
Kwun
Chi Hwa
CH
Kim
Jin Young
JY
Lee
Yeon Joo
YJ
Yook
Ah-Ra
AR
Ko
Dong-Kyu
DK
Jin
D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D056947:Enzyme Replacement Therapy; D005347:Fibroblasts / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D007066:Iduronate Sulfatase / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D008360:Mannosephosphates / Q000737:chemistry; D016532:Mucopolysaccharidosis II / Q000628:therapy; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology
D008360:Mannosephosphates; D011993:Recombinant Fusion Proteins; C027693:mannose-6-phosphate; C524739:C(alpha)-formylglycine; D007066:Iduronate Sulfatase; C517982:idursulfase; D019158:N-Acetylneuraminic Acid; D000409:Alanine; D005998:Glycine