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A biochemical and physicochemical comparison of two recombinant enzymes used for enzyme replacement therapies of hunter syndrome

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Abstract

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.

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Acknowledgments

This study was sponsored by Green Cross Corp. (Yongin, Korea). This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A101779). We thank Myeong-suk Moon and Jun-mo Bae for helpful supporting on specific enzyme activity assay and in vitro cell uptake assay.

All of the authors have nothing to disclose.

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Authors and Affiliations

  1. Department of Molecular Science and Technology, Ajou University, Suwon, South Korea

    Yo Kyung Chung

  2. Bioprocess Engineering, Central Research Center, Green Cross Corporation, Yongin, South Korea

    Yo Kyung Chung & Jong Mun Sohn

  3. Department of Medical Genetics, Ajou University School of Medicine, Suwon, South Korea

    Young Bae Sohn

  4. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-ku, 135-710, Seoul, South Korea

    Jieun Lee, Mi Sun Chang, Younghee Kwun & Dong-Kyu Jin

  5. Rare Diesase Team, Mogam Biotechnology Research Institute, Yongin, South Korea

    Chi Hwa Kim

  6. Clinical Research Center, Samsung Biomedical Research Institute, Seoul, South Korea

    Jin Young Lee, Yeon Joo Yook & Ah-Ra Ko

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  1. Yo Kyung Chung
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  3. Jong Mun Sohn
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Correspondence to Dong-Kyu Jin.

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Yo Kyung Chung and Young Bae Sohn were equally contributed to this work.

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Chung, Y.K., Sohn, Y.B., Sohn, J.M. et al. A biochemical and physicochemical comparison of two recombinant enzymes used for enzyme replacement therapies of hunter syndrome. Glycoconj J 31, 309–315 (2014). https://doi.org/10.1007/s10719-014-9523-0

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  • DOI: https://doi.org/10.1007/s10719-014-9523-0

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