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

Issue title: Promoting Bone Health in MPS VI (Maroteaux-Lamy Syndrome): Framing New Therapies, Part 2

Article type: Research Article

Authors: Decker, Celeste | Yu, Zi-Fan | Giugliani, Roberto | Schwartz, Ida Vanessa D. | Guffon, Nathalie | Teles, Elisa Leão | 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 | Paul Harmatz for the MPS VI Study Group,

Affiliations: BioMarin Pharmaceutical Inc, Novato, CA, USA | Statistics Collaborative, Inc., Washington, DC, USA | Serviço de Genética Médica/ HCPA and Department of Genetics/UFRGS, Porto Alegre, Brazil | Hôpital Femme Mère Enfant, Service Maladies Métaboliques, BRON, France | Unidade de Doenças Metabólicas, Departamento Pediatria, Hospital de Sao João, Porto, Portugal | Unidade de Biologia do Lisossoma e Peroxisoma, Instituto de Biologia Molecular e Celular, Porto, Portugal | Royal Manchester Children's Hospital, Manchester, UK | Children's Hospital, University of Mainz, Germany | Department of Pediatrics, University of Padova, Padova, Italy | SA Pathology at Women's and Children's Hospital, North Adelaide, Australia | Department of Genetic Medicine, Women's and Children's Hospital Adelaide, North Adelaide, Australia | University Klinik für Kinder und Jugendheilkunde, Graz, Austria | epartments of Pediatrics and Molecular and Medical Genetics, Oregon Health &} Science University, Portland, OR, USA | University of Minnesota Medical School, Minneapolis, MN, USA | Children's Hospital of Philadelphia, Philadelphia, PA, USA | Children's Hospital & Research Center Oakland, Oakland, CA, USA

Note: [] Address for correspondence: Paul Harmatz, MD, Children's Hospital & Research Center Oakland, 747 52{nd} Street, Oakland, CA 94609, USA. Tel.: +1 510 428 3058; Fax: +1 510 450 5813; E-mail: Pharmatz@mail.cho.org

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

DOI: 10.3233/PRM-2010-0113

Journal: Journal of Pediatric Rehabilitation Medicine, vol. 3, no. 2, pp. 89-100, 2010

Received 18 March 2010
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Accepted 18 March 2010
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Published: 2010
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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.

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