Comparative study on mannose 6-phosphate residue contents of recombinant lysosomal enzymes

Togawa, Tadayasu; Takada, Moriatsu; Aizawa, Yoshiaki; Tsukimura, Takahiro; Chiba, Yasunori; Sakuraba, Hitoshi

doi:10.1016/j.ymgme.2013.12.296

Cited by 29 publications

(22 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Agalsidase alfa and agalsidase beta have identical amino acid sequences and are functionally equivalent (Lee et al 2003). However, agalsidase beta contains more fully sialylated oligosaccharides and more mannose-6-phosphate than agalsidase alfa (Lee et al 2003;Togawa et al 2014); cellular uptake of recombinant agalsidases is mediated by mannose-6-phosphate receptors. Greater uptake of agalsidase beta than of agalsidase alfa has been suggested in vitro (in skin fibroblasts from patients with FD) (Keslová-Veselíková et al 2008;Lee et al 2003) and in vivo (in the kidney and heart after administration of the same dose of the two enzymes in a mouse model of FD) (Desnick and Schuchman 2012;Sakuraba et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Reduction of Plasma Globotriaosylsphingosine Levels After Switching from Agalsidase Alfa to Agalsidase Beta as Enzyme Replacement Therapy for Fabry Disease

Göker-Alpan

Gambello

Maegawa³

et al. 2015

JIMD Reports

View full text Add to dashboard Cite

Introduction: Agalsidase alfa and agalsidase beta, recombinant enzyme preparations for treatment of Fabry disease (FD), have different approved dosing schedules: 0.2 mg/kg and 1.0 mg/kg every other week (EOW), respectively.Methods: This open-label, multicenter, exploratory phase 4 study evaluated plasma globotriaosylsphingosine (lyso-GL-3) and plasma and urine globotriaosylceramide (GL-3) levels at baseline and 2, 4, and 6 months after the switch from agalsidase alfa (0.2 mg/kg EOW for !12 months) to agalsidase beta (1.0 mg/kg EOW) in 15 male patients with FD. Immunoglobulin (Ig)G antidrug antibody titers were assessed, and safety was monitored throughout the study.Results: Plasma lyso-GL-3 concentrations decreased significantly within 2 months after switch and reductions continued through month 6 (mean absolute changes, À12.8, À16.1, and À16.7 ng/mL at 2, 4, and 6 months, respectively; all P < 0.001). The mean percentage reduction from baseline was 39.5% (P < 0.001) at month 6. For plasma GL-3, the mean absolute change from baseline (À0.9 mg/mL) and percentage reduction (17.9%) at month 6 were both significant (P < 0.05). Urine GL-3 measurements showed intra-patient variability and changes from baseline were not significant. No clinical outcomes were assessed in this 6-month study, and, therefore, no conclusions can be drawn regarding the correlation of observed reductions in glycosphingolipid concentrations with clinically relevant outcomes. There were no differences in IgG antidrug antibody titers between the two enzymes. The switch from agalsidase alfa to agalsidase beta was well tolerated.Conclusion: Plasma lyso-GL-3 and GL-3 levels reduced after switching from agalsidase alfa to agalsidase beta, indicating that agalsidase beta has a greater pharmacodynamic effect on these markers at the recommended dose. These data further support the use of agalsidase beta 1.0 mg/kg EOW as enzyme replacement therapy in FD.

show abstract

Section: Introductionmentioning

confidence: 99%

Reduction of Plasma Globotriaosylsphingosine Levels After Switching from Agalsidase Alfa to Agalsidase Beta as Enzyme Replacement Therapy for Fabry Disease

Göker-Alpan

Gambello

Maegawa³

et al. 2015

JIMD Reports

View full text Add to dashboard Cite

show abstract

“…In the USA, agalsidase beta (Fabrazyme ® ; Genzyme, a Sanofi company) is the only ERT approved to treat FD. However, agalsidase beta contains more fully sialylated oligosaccharides and more mannose-6-phosphate than agalsidase alfa (Lee et al 2003;Togawa et al 2014); cellular uptake of recombinant agalsidases is mediated by mannose-6-phosphate receptors. Agalsidase alfa and agalsidase beta have identical amino acid sequences and are functionally equivalent (Lee et al 2003).…”

Section: Discussionmentioning

confidence: 99%

JIMD Reports, Volume 25

Morava¹,

Baumgartner²,

Patterson³

et al. 2016

JIMD Reports

View full text Add to dashboard Cite

“…However, significant differences in therapeutic efficacies were not observed in a small clinical study (34 Fabry disease patients) with the treatment of either Agalsidase alfa or Agalsidase beta at the same dose (0.2 mg/kg) (15) . These results may be related to the marginal difference in M-6-P contents between the two GLAs, which was revealed by a recent comparative study of the M-6-P contents of six therapeutic enzymes (16) , with the M-6-P contents of Agalsidase alfa and Agalsidase beta being 2.1 and 2.9 mol/mol enzyme, respectively.…”

Section: Introductionmentioning

confidence: 93%

“… *The values of M-6-P content (mol/mol enzyme) were obtained from a comparative study (16) . Gb3: Globotriaosylceramide, MPS: Mucopolysaccharidosis, DS: Dematan sulfate, HS: Heparan sulfate, KS: Keratan sulfate, C6S: Chondrotin 6-sulfate, C4S: Chondrotin 4-sulfate.…”

Section: Introductionmentioning

confidence: 99%

Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases

2015

BMB Reports

View full text Add to dashboard Cite

Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized by massive accumulation of undigested compounds in lysosomes, which is caused by genetic defects resulting in the deficiency of a lysosomal hydrolase. Currently, enzyme replacement therapy has been successfully used for treatment of 7 LSDs with 10 approved therapeutic enzymes whereas new approaches such as pharmacological chaperones and gene therapy still await evaluation in clinical trials. While therapeutic enzymes for Gaucher disease have N-glycans with terminal mannose residues for targeting to macrophages, the others require N-glycans containing mannose-6-phosphates that are recognized by mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic enzymes is essential for the clearance of accumulated compounds, the suitable glycan structure and its high content are key factors for efficient therapeutic efficacy. Therefore, glycan remodeling strategies to improve lysosomal targeting and tissue distribution have been highlighted. This review describes the glycan structures that are important for lysosomal targeting and provides information on recent glyco-engineering technologies for the development of therapeutic enzymes with improved efficacy. [BMB Reports 2015; 48(8): 438-444]

show abstract

Comparative study on mannose 6-phosphate residue contents of recombinant lysosomal enzymes

Cited by 29 publications

References 30 publications

Reduction of Plasma Globotriaosylsphingosine Levels After Switching from Agalsidase Alfa to Agalsidase Beta as Enzyme Replacement Therapy for Fabry Disease

Reduction of Plasma Globotriaosylsphingosine Levels After Switching from Agalsidase Alfa to Agalsidase Beta as Enzyme Replacement Therapy for Fabry Disease

JIMD Reports, Volume 25

Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases

Contact Info

Product

Resources

About