Enzyme replacement therapy for mucopolysaccharidosis VI: Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase

Celeste Decker, Zi Fan Yu, Roberto Giugliani, Ida Vanessa D Schwartz, Nathalie Guffon, Elisa Leo Teles, M. Clara Sá Miranda, J. Edmond Wraith, Michael Beck, Laila Arash, Maurizio Scarpa, David Ketteridge, John J. Hopwood, Barbara Plecko, Robert Steiner, Chester B. Whitley, Paige Kaplan, Stuart J. Swiedler, Susan Conrad, Paul Harmatz

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Background and Methods: Growth failure is characteristic of untreated mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome). Growth was studied in fifty-six MPS VI patients (5 to 29 years old) prior to and for up to 240 weeks of weekly infusions of recombinant human arylsulfatase B (rhASB) at 1 mg/kg during Phase 1/2, Phase 2, Phase 3 or Phase 3 Extension clinical trials. Height, weight, and Tanner stage data were collected. Pooled data were analyzed to determine mean height increase by treatment week, growth impacts of pubertal status, baseline urinary GAG, and age at treatment initiation. Growth rate for approximately 2 years prior to and following treatment initiation was analyzed using longitudinal modeling. Results: Mean height increased by 2.9 cm after 48 weeks and 4.3 cm after 96 weeks on enzyme replacement therapy (ERT). Growth on ERT was not correlated with baseline urinary GAG. Patients under 16~years of age showed greatest increases in height on treatment. Model results based on pooled data showed significant improvement in growth rate during 96~weeks of ERT when compared to the equivalent pretreatment time period. Delayed pubertal onset or progression was noted in 10 patients entering the clinical trials; all of whom showed progression of at least one Tanner stage during 2 years on ERT, and 6 of whom (60%) completed puberty. Conclusion: Analysis of mean height by treatment week and longitudinal modeling demonstrate significant increase in height and growth rate in MPS VI patients receiving long-term ERT. This impact was greatest in patients aged below 16 years. Height increase may result from bone growth and/or reduction in joint contractures. Bone growth and resolution of delayed puberty may be related to improvements in general health, bone cell health, nutrition, endocrine gland function and reduced inflammation.

LanguageEnglish
Pages89-100
Number of pages12
JournalJournal of Pediatric Rehabilitation Medicine
Volume3
Issue number2
DOIs
Publication statusPublished - 21 Jul 2010

Keywords

  • Mucopolysaccharidosis VI
  • N$-acetylgalactosamine 4-sulfatase
  • arylsulfatase B
  • enzyme replacement therapy
  • glycosaminoglycans
  • growth
  • puberty

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Physical Therapy, Sports Therapy and Rehabilitation
  • Rehabilitation

Cite this

Decker, Celeste ; Yu, Zi Fan ; Giugliani, Roberto ; Schwartz, Ida Vanessa D ; Guffon, Nathalie ; Teles, Elisa Leo ; Miranda, M. Clara Sá ; Wraith, J. Edmond ; Beck, Michael ; Arash, Laila ; Scarpa, Maurizio ; Ketteridge, David ; Hopwood, John J. ; Plecko, Barbara ; Steiner, Robert ; Whitley, Chester B. ; Kaplan, Paige ; Swiedler, Stuart J. ; Conrad, Susan ; Harmatz, Paul. / Enzyme replacement therapy for mucopolysaccharidosis VI : Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase. In: Journal of Pediatric Rehabilitation Medicine. 2010 ; Vol. 3, No. 2. pp. 89-100.
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title = "Enzyme replacement therapy for mucopolysaccharidosis VI: Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase",
abstract = "Background and Methods: Growth failure is characteristic of untreated mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome). Growth was studied in fifty-six MPS VI patients (5 to 29 years old) prior to and for up to 240 weeks of weekly infusions of recombinant human arylsulfatase B (rhASB) at 1 mg/kg during Phase 1/2, Phase 2, Phase 3 or Phase 3 Extension clinical trials. Height, weight, and Tanner stage data were collected. Pooled data were analyzed to determine mean height increase by treatment week, growth impacts of pubertal status, baseline urinary GAG, and age at treatment initiation. Growth rate for approximately 2 years prior to and following treatment initiation was analyzed using longitudinal modeling. Results: Mean height increased by 2.9 cm after 48 weeks and 4.3 cm after 96 weeks on enzyme replacement therapy (ERT). Growth on ERT was not correlated with baseline urinary GAG. Patients under 16~years of age showed greatest increases in height on treatment. Model results based on pooled data showed significant improvement in growth rate during 96~weeks of ERT when compared to the equivalent pretreatment time period. Delayed pubertal onset or progression was noted in 10 patients entering the clinical trials; all of whom showed progression of at least one Tanner stage during 2 years on ERT, and 6 of whom (60{\%}) completed puberty. Conclusion: Analysis of mean height by treatment week and longitudinal modeling demonstrate significant increase in height and growth rate in MPS VI patients receiving long-term ERT. This impact was greatest in patients aged below 16 years. Height increase may result from bone growth and/or reduction in joint contractures. Bone growth and resolution of delayed puberty may be related to improvements in general health, bone cell health, nutrition, endocrine gland function and reduced inflammation.",
keywords = "Mucopolysaccharidosis VI, N$-acetylgalactosamine 4-sulfatase, arylsulfatase B, enzyme replacement therapy, glycosaminoglycans, growth, puberty",
author = "Celeste Decker and Yu, {Zi Fan} and Roberto Giugliani and Schwartz, {Ida Vanessa D} and Nathalie Guffon and Teles, {Elisa Leo} and Miranda, {M. Clara S{\'a}} and Wraith, {J. Edmond} and Michael Beck and Laila Arash and Maurizio Scarpa and David Ketteridge and Hopwood, {John J.} and Barbara Plecko and Robert Steiner and Whitley, {Chester B.} and Paige Kaplan and Swiedler, {Stuart J.} and Susan Conrad and Paul Harmatz",
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Decker, C, Yu, ZF, Giugliani, R, Schwartz, IVD, Guffon, N, Teles, EL, Miranda, MCS, Wraith, JE, Beck, M, Arash, L, Scarpa, M, Ketteridge, D, Hopwood, JJ, Plecko, B, Steiner, R, Whitley, CB, Kaplan, P, Swiedler, SJ, Conrad, S & Harmatz, P 2010, 'Enzyme replacement therapy for mucopolysaccharidosis VI: Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase', Journal of Pediatric Rehabilitation Medicine, vol. 3, no. 2, pp. 89-100. https://doi.org/10.3233/PRM-2010-0113

Enzyme replacement therapy for mucopolysaccharidosis VI : Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase. / Decker, Celeste; Yu, Zi Fan; Giugliani, Roberto; Schwartz, Ida Vanessa D; Guffon, Nathalie; Teles, Elisa Leo; Miranda, M. Clara Sá; Wraith, J. Edmond; Beck, Michael; Arash, Laila; Scarpa, Maurizio; Ketteridge, David; Hopwood, John J.; Plecko, Barbara; Steiner, Robert; Whitley, Chester B.; Kaplan, Paige; Swiedler, Stuart J.; Conrad, Susan; Harmatz, Paul.

In: Journal of Pediatric Rehabilitation Medicine, Vol. 3, No. 2, 21.07.2010, p. 89-100.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Enzyme replacement therapy for mucopolysaccharidosis VI

T2 - Journal of Pediatric Rehabilitation Medicine

AU - Decker, Celeste

AU - Yu, Zi Fan

AU - Giugliani, Roberto

AU - Schwartz, Ida Vanessa D

AU - Guffon, Nathalie

AU - Teles, Elisa Leo

AU - Miranda, M. Clara Sá

AU - Wraith, J. Edmond

AU - Beck, Michael

AU - Arash, Laila

AU - Scarpa, Maurizio

AU - Ketteridge, David

AU - Hopwood, John J.

AU - Plecko, Barbara

AU - Steiner, Robert

AU - Whitley, Chester B.

AU - Kaplan, Paige

AU - Swiedler, Stuart J.

AU - Conrad, Susan

AU - Harmatz, Paul

PY - 2010/7/21

Y1 - 2010/7/21

N2 - Background and Methods: Growth failure is characteristic of untreated mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome). Growth was studied in fifty-six MPS VI patients (5 to 29 years old) prior to and for up to 240 weeks of weekly infusions of recombinant human arylsulfatase B (rhASB) at 1 mg/kg during Phase 1/2, Phase 2, Phase 3 or Phase 3 Extension clinical trials. Height, weight, and Tanner stage data were collected. Pooled data were analyzed to determine mean height increase by treatment week, growth impacts of pubertal status, baseline urinary GAG, and age at treatment initiation. Growth rate for approximately 2 years prior to and following treatment initiation was analyzed using longitudinal modeling. Results: Mean height increased by 2.9 cm after 48 weeks and 4.3 cm after 96 weeks on enzyme replacement therapy (ERT). Growth on ERT was not correlated with baseline urinary GAG. Patients under 16~years of age showed greatest increases in height on treatment. Model results based on pooled data showed significant improvement in growth rate during 96~weeks of ERT when compared to the equivalent pretreatment time period. Delayed pubertal onset or progression was noted in 10 patients entering the clinical trials; all of whom showed progression of at least one Tanner stage during 2 years on ERT, and 6 of whom (60%) completed puberty. Conclusion: Analysis of mean height by treatment week and longitudinal modeling demonstrate significant increase in height and growth rate in MPS VI patients receiving long-term ERT. This impact was greatest in patients aged below 16 years. Height increase may result from bone growth and/or reduction in joint contractures. Bone growth and resolution of delayed puberty may be related to improvements in general health, bone cell health, nutrition, endocrine gland function and reduced inflammation.

AB - Background and Methods: Growth failure is characteristic of untreated mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome). Growth was studied in fifty-six MPS VI patients (5 to 29 years old) prior to and for up to 240 weeks of weekly infusions of recombinant human arylsulfatase B (rhASB) at 1 mg/kg during Phase 1/2, Phase 2, Phase 3 or Phase 3 Extension clinical trials. Height, weight, and Tanner stage data were collected. Pooled data were analyzed to determine mean height increase by treatment week, growth impacts of pubertal status, baseline urinary GAG, and age at treatment initiation. Growth rate for approximately 2 years prior to and following treatment initiation was analyzed using longitudinal modeling. Results: Mean height increased by 2.9 cm after 48 weeks and 4.3 cm after 96 weeks on enzyme replacement therapy (ERT). Growth on ERT was not correlated with baseline urinary GAG. Patients under 16~years of age showed greatest increases in height on treatment. Model results based on pooled data showed significant improvement in growth rate during 96~weeks of ERT when compared to the equivalent pretreatment time period. Delayed pubertal onset or progression was noted in 10 patients entering the clinical trials; all of whom showed progression of at least one Tanner stage during 2 years on ERT, and 6 of whom (60%) completed puberty. Conclusion: Analysis of mean height by treatment week and longitudinal modeling demonstrate significant increase in height and growth rate in MPS VI patients receiving long-term ERT. This impact was greatest in patients aged below 16 years. Height increase may result from bone growth and/or reduction in joint contractures. Bone growth and resolution of delayed puberty may be related to improvements in general health, bone cell health, nutrition, endocrine gland function and reduced inflammation.

KW - Mucopolysaccharidosis VI

KW - N$-acetylgalactosamine 4-sulfatase

KW - arylsulfatase B

KW - enzyme replacement therapy

KW - glycosaminoglycans

KW - growth

KW - puberty

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