Correction of CNS Defects in the MPSII Mouse Model Via Systemic Enzyme Replacement Therapy

Overview

Journal Hum Mol Genet

Specialties Genetics
Molecular Biology

Date 2010 Sep 30

PMID 20876612

Citations 25

Authors

Vinicia Assunta Polito

Serena Abbondante

Roman S Polishchuk

Edoardo Nusco

Rosaria Salvia

Maria Pia Cosma

Affiliations

Soon will be listed here.

Abstract

Mucopolysaccharidosis type II (MPSII), or Hunter syndrome, is a devastating disorder associated with a shortened life expectancy. Patients affected by MPSII have a variety of symptoms that affect all organs of the body and may include progressive cognitive impairment. MPSII is due to inactivity of the enzyme iduronate-2-sulfatase (IDS), which results in the accumulation of storage material in the lysosomes, such as dermatan and heparan sulfates, with consequent cell degeneration in all tissues including, in the severe phenotype, neurodegeneration in the central nervous system (CNS). To date, the only treatment available is systemic infusion of IDS, which ameliorates exclusively certain visceral defects. Therefore, it is important to simultaneously treat the visceral and CNS defects of the MPSII patients. Here, we have developed enzyme replacement therapy (ERT) protocols in a mouse model that allow the IDS to reach the brain, with the substantial correction of the CNS phenotype and of the neurobehavioral features. Treatments were beneficial even in adult and old MPSII mice, using relatively low doses of infused IDS over long intervals. This study demonstrates that CNS defects of MPSII mice can be treated by systemic ERT, providing the potential for development of an effective treatment for MPSII patients.

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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

Muenzer J, Gucsavas-Calikoglu M, McCandless S, Schuetz T, Kimura A . A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. 2006; 90(3):329-37. DOI: 10.1016/j.ymgme.2006.09.001. View

Muenzer J, Wraith J, Beck M, Giugliani R, Harmatz P, Eng C . A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006; 8(8):465-73. DOI: 10.1097/01.gim.0000232477.37660.fb. View

Archer I, Harper P, Wusteman F . Multiple forms of iduronate 2-sulphate sulphatase in human tissues and body fluids. Biochim Biophys Acta. 1982; 708(2):134-40. DOI: 10.1016/0167-4838(82)90213-8. View

Bronikowski A, Carter P, Swallow J, Girard I, Rhodes J, Garland Jr T . Open-field behavior of house mice selectively bred for high voluntary wheel-running. Behav Genet. 2001; 31(3):309-16. DOI: 10.1023/a:1012283426530. View

Roces D, Lullmann-Rauch R, Peng J, Balducci C, Andersson C, Tollersrud O . Efficacy of enzyme replacement therapy in alpha-mannosidosis mice: a preclinical animal study. Hum Mol Genet. 2004; 13(18):1979-88. DOI: 10.1093/hmg/ddh220. View

Barton N, Brady R, Dambrosia J, Di Bisceglie A, Doppelt S, Hill S . Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med. 1991; 324(21):1464-70. DOI: 10.1056/NEJM199105233242104. View

MCKUSICK V . The relative frequency of the Hurler and Hunter syndromes. N Engl J Med. 1970; 283(16):853-4. DOI: 10.1056/NEJM197010152831606. View

Weinreb N, Charrow J, Andersson H, Kaplan P, Kolodny E, Mistry P . Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Registry. Am J Med. 2002; 113(2):112-9. DOI: 10.1016/s0002-9343(02)01150-6. View

10.

Schuchman E . The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. J Inherit Metab Dis. 2007; 30(5):654-63. DOI: 10.1007/s10545-007-0632-9. View

11.

Voznyi Y, Keulemans J, van Diggelen O . A fluorimetric enzyme assay for the diagnosis of MPS II (Hunter disease). J Inherit Metab Dis. 2002; 24(6):675-80. DOI: 10.1023/a:1012763026526. View

12.

Eng C, Guffon N, Wilcox W, Germain D, Lee P, Waldek S . Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease. N Engl J Med. 2001; 345(1):9-16. DOI: 10.1056/NEJM200107053450102. View

13.

Wraith J, Clarke L, Beck M, Kolodny E, Pastores G, Muenzer J . Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr. 2004; 144(5):581-8. DOI: 10.1016/j.jpeds.2004.01.046. View

14.

Wilson P, Suthers G, Callen D, Baker E, Nelson P, Cooper A . Frequent deletions at Xq28 indicate genetic heterogeneity in Hunter syndrome. Hum Genet. 1991; 86(5):505-8. DOI: 10.1007/BF00194643. View

15.

Orii K, Grubb J, Vogler C, Levy B, Tan Y, Markova K . Defining the pathway for Tat-mediated delivery of beta-glucuronidase in cultured cells and MPS VII mice. Mol Ther. 2005; 12(2):345-52. PMC: 2587041. DOI: 10.1016/j.ymthe.2005.02.031. View

16.

Silva R, Gordon S . Phagocytosis stimulates alternative glycosylation of macrosialin (mouse CD68), a macrophage-specific endosomal protein. Biochem J. 1999; 338 ( Pt 3):687-94. PMC: 1220104. View

17.

Harmatz P, Ketteridge D, Giugliani R, Guffon N, Leao Teles E, Clara Sa Miranda M . Direct comparison of measures of endurance, mobility, and joint function during enzyme-replacement therapy of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): results after 48 weeks in a phase 2 open-label clinical study of recombinant human.... Pediatrics. 2005; 115(6):e681-9. DOI: 10.1542/peds.2004-1023. View

18.

Lissens W, Seneca S, Liebaers I . Molecular analysis in 23 Hunter disease families. J Inherit Metab Dis. 1997; 20(3):453-6. DOI: 10.1023/a:1005335624386. View

19.

Tanzer F, Buyukkayhan D, Cansu Mutlu E, Kalender Korkmaz F . Enzyme replacement therapy in an infant with Pompe's disease with severe cardiomyopathy. J Pediatr Endocrinol Metab. 2010; 22(12):1159-62. DOI: 10.1515/jpem.2009.22.12.1159. View

20.

Timms K, Bondeson M, Ansari-Lari M, Lagerstedt K, Muzny D, Nelson D . Molecular and phenotypic variation in patients with severe Hunter syndrome. Hum Mol Genet. 1997; 6(3):479-86. DOI: 10.1093/hmg/6.3.479. View