TY - JOUR
T1 - Enzyme replacement therapy for mucopolysaccharidosis VI
T2 - Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase
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
Y1 - 2010
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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U2 - 10.3233/PRM-2010-0113
DO - 10.3233/PRM-2010-0113
M3 - Article
C2 - 20634905
AN - SCOPUS:77954629021
SN - 1874-5393
VL - 3
SP - 89
EP - 100
JO - Journal of Pediatric Rehabilitation Medicine
JF - Journal of Pediatric Rehabilitation Medicine
IS - 2
ER -