Effect of Enzyme Replacement Therapy on the Growth of Patients with Morquio A

Overview

Journal J Hum Genet

Specialty Genetics

Date 2019 Apr 26

PMID 31019230

Citations 31

Authors

Caitlin Doherty

Molly Stapleton

Matthew Piechnik

Robert W Mason

William G Mackenzie

Seiji Yamaguchi

Hironori Kobayashi

Yasuyuki Suzuki

Shunji Tomatsu

Affiliations

Soon will be listed here.

Abstract

Mucopolysaccharidosis IVA (MPS IVA) is a degenerative systemic skeletal dysplasia, in which children exhibit marked short stature and become physically handicapped. This study evaluated the growth patterns of patients treated with enzyme replacement therapy (ERT), compared with those of untreated patients. Cross-sectional and longitudinal data of heights and weights were collected from 128 MPS IVA patients and compared with the growth charts of MPS IVA. Twelve patients (six males, six females) starting ERT before 5 years old were treated for at least 2 years. Six out of 12 patients (50%) with ERT over 2 years stopped growing between 94 and 98 cm (mean height of 95.1 ± 2.2 cm) from 5.0 years to 9.0 years of age (mean age of 6.2 ± 1.6 years). The other patients, except one attenuated case, exhibited a marked slow growth velocity from 3.6 years to 7.7 years. Treated and untreated patients with severe phenotype reached their final heights by ~10 years of age. Patients treated with ERT exhibited a reduced pubertal growth spurt analogous to their untreated counterparts, which contributes to the marked short stature associated with MPS IVA. Compared with the growth charts for untreated patients, patients treated with ERT did not show any significant increase in growth in any age group. Overall, ERT-treated patients do not experience growth improvement and continue to exhibit poor growth despite early ERT intervention before 5 years of age. These findings indicate that current intravenous ERT is ineffective at correcting abnormal growth in MPS IVA.

Citing Articles

Adeno-Associated Virus Gene Transfer Ameliorates Progression of Skeletal Lesions in Mucopolysaccharidosis IVA Mice.

Herreno-Pachon A, Sawamoto K, Stapleton M, Khan S, Piechnik M, Alvarez J Hum Gene Ther. 2024; 35(23-24):955-968.

PMID: 39450470 PMC: 11659441. DOI: 10.1089/hum.2024.096.

Hematopoietic stem cell transplantation in children with mucopolysaccharidosis IVA: single center experience.

Yalcin K, Uygun V, Ozturk Hismi B, Celen S, Ozturkmen S, Zhumatayev S Bone Marrow Transplant. 2024; 60(1):47-51.

PMID: 39402187 DOI: 10.1038/s41409-024-02439-4.

Potential Targeting Mechanisms for Bone-Directed Therapies.

Celik B, Leal A, Tomatsu S Int J Mol Sci. 2024; 25(15).

PMID: 39125906 PMC: 11312506. DOI: 10.3390/ijms25158339.

Molecular therapy and nucleic acid adeno-associated virus-based gene therapy delivering combinations of two growth-associated genes to MPS IVA mice.

Rintz E, Celik B, Fnu N, Herreno-Pachon A, Khan S, Benincore-Florez E Mol Ther Nucleic Acids. 2024; 35(2):102211.

PMID: 38831899 PMC: 11145352. DOI: 10.1016/j.omtn.2024.102211.

Growth patterns in patients with mucopolysaccharidosis VII.

Montano A, Rozdzynska-Swiatkowska A, Jurecka A, Ramirez A, Zhang L, Marsden D Mol Genet Metab Rep. 2023; 36:100987.

PMID: 37415957 PMC: 10320588. DOI: 10.1016/j.ymgmr.2023.100987.

References

Wraith J, Scarpa M, Beck M, Bodamer O, De Meirleir L, Guffon N . Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2007; 167(3):267-77. PMC: 2234442. DOI: 10.1007/s00431-007-0635-4. View

Jones S, Bialer M, Parini R, Martin K, Wang H, Yang K . Safety and clinical activity of elosulfase alfa in pediatric patients with Morquio A syndrome (mucopolysaccharidosis IVA) less than 5 y. Pediatr Res. 2015; 78(6):717-22. PMC: 4700045. DOI: 10.1038/pr.2015.169. View

Tomatsu S, Sawamoto K, Shimada T, Bober M, Kubaski F, Yasuda E . Enzyme replacement therapy for treating mucopolysaccharidosis type IVA (Morquio A syndrome): effect and limitations. Expert Opin Orphan Drugs. 2016; 3(11):1279-1290. PMC: 4788508. DOI: 10.1517/21678707.2015.1086640. View

Applegarth D, Toone J, Lowry R . Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. 2000; 105(1):e10. DOI: 10.1542/peds.105.1.e10. View

Hendriksz C, Burton B, Fleming T, Harmatz P, Hughes D, Jones S . Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study. J Inherit Metab Dis. 2014; 37(6):979-90. PMC: 4206772. DOI: 10.1007/s10545-014-9715-6. View

Khan S, Peracha H, Ballhausen D, Wiesbauer A, Rohrbach M, Gautschi M . Epidemiology of mucopolysaccharidoses. Mol Genet Metab. 2017; 121(3):227-240. PMC: 5653283. DOI: 10.1016/j.ymgme.2017.05.016. View

Khan S, Mason R, Giugliani R, Orii K, Fukao T, Suzuki Y . Glycosaminoglycans analysis in blood and urine of patients with mucopolysaccharidosis. Mol Genet Metab. 2018; 125(1-2):44-52. PMC: 6175648. DOI: 10.1016/j.ymgme.2018.04.011. View

Tomatsu S, Averill L, Sawamoto K, Mackenzie W, Bober M, Pizarro C . Obstructive airway in Morquio A syndrome, the past, the present and the future. Mol Genet Metab. 2015; 117(2):150-6. PMC: 4755902. DOI: 10.1016/j.ymgme.2015.09.007. View

Hendriksz C, Harmatz P, Beck M, Jones S, Wood T, Lachman R . Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA. Mol Genet Metab. 2013; 110(1-2):54-64. PMC: 3755102. DOI: 10.1016/j.ymgme.2013.04.002. View

10.

Doherty C, Averill L, Theroux M, Mackenzie W, Pizarro C, Mason R . Natural history of Morquio A patient with tracheal obstruction from birth to death. Mol Genet Metab Rep. 2018; 14:59-67. PMC: 5758848. DOI: 10.1016/j.ymgmr.2017.11.005. View

11.

Chinen Y, Higa T, Tomatsu S, Suzuki Y, Orii T, Hyakuna N . Long-term therapeutic efficacy of allogenic bone marrow transplantation in a patient with mucopolysaccharidosis IVA. Mol Genet Metab Rep. 2015; 1:31-41. PMC: 4292891. DOI: 10.1016/j.ymgmr.2013.11.002. View

12.

Montano A, Tomatsu S, Gottesman G, Smith M, Orii T . International Morquio A Registry: clinical manifestation and natural course of Morquio A disease. J Inherit Metab Dis. 2007; 30(2):165-74. DOI: 10.1007/s10545-007-0529-7. View

13.

Tomatsu S, Montano A, Oikawa H, Smith M, Barrera L, Chinen Y . Mucopolysaccharidosis type IVA (Morquio A disease): clinical review and current treatment. Curr Pharm Biotechnol. 2011; 12(6):931-45. DOI: 10.2174/138920111795542615. View

14.

Do Cao J, Wiedemann A, Quinaux T, Battaglia-Hsu S, Mainard L, Froissart R . 30 months follow-up of an early enzyme replacement therapy in a severe Morquio A patient: About one case. Mol Genet Metab Rep. 2016; 9:42-45. PMC: 5065040. DOI: 10.1016/j.ymgmr.2016.10.001. View

15.

Sekido T, Sakura N, Higashi Y, Miya K, Nitta Y, Nomura M . Novel drug delivery system to bone using acidic oligopeptide: pharmacokinetic characteristics and pharmacological potential. J Drug Target. 2001; 9(2):111-21. DOI: 10.3109/10611860108997922. View

16.

Tomatsu S, Almeciga-Diaz C, Montano A, Yabe H, Tanaka A, Dung V . Therapies for the bone in mucopolysaccharidoses. Mol Genet Metab. 2014; 114(2):94-109. PMC: 4312706. DOI: 10.1016/j.ymgme.2014.12.001. View

17.

Yasuda E, Suzuki Y, Shimada T, Sawamoto K, Mackenzie W, Theroux M . Activity of daily living for Morquio A syndrome. Mol Genet Metab. 2016; 118(2):111-22. PMC: 5016714. DOI: 10.1016/j.ymgme.2016.04.005. View

18.

Qi Y, Musson D, Schweighardt B, Tompkins T, Jesaitis L, Shaywitz A . Pharmacokinetic and pharmacodynamic evaluation of elosulfase alfa, an enzyme replacement therapy in patients with Morquio A syndrome. Clin Pharmacokinet. 2014; 53(12):1137-47. PMC: 4243006. DOI: 10.1007/s40262-014-0173-y. View

19.

Nishioka T, Tomatsu S, Gutierrez M, Miyamoto K, Trandafirescu G, Lopez P . Enhancement of drug delivery to bone: characterization of human tissue-nonspecific alkaline phosphatase tagged with an acidic oligopeptide. Mol Genet Metab. 2006; 88(3):244-55. PMC: 2587042. DOI: 10.1016/j.ymgme.2006.02.012. View

20.

Tomatsu S, Montano A, Dung V, Ohashi A, Oikawa H, Oguma T . Enhancement of drug delivery: enzyme-replacement therapy for murine Morquio A syndrome. Mol Ther. 2010; 18(6):1094-102. PMC: 2889747. DOI: 10.1038/mt.2010.32. View