Enzyme replacement therapy in mucopolysaccharidosis VI (Maroteaux-Lamy syndrome).

Abstract

OBJECTIVES:

To evaluate the safety and efficacy of weekly treatment with human recombinant N-acetylgalactosamine 4-sulfatase (rhASB) in humans with mucopolysaccharidosis type VI (MPS VI).

STUDY DESIGN:

An ongoing Phase I/II, randomized, two-dose, double-blind study. Patients were randomized to weekly infusions of either high (1.0 mg/kg) or low (0.2 mg/kg) doses of rhASB. Six patients (3 male, 3 female; age 7-16 years) completed at least 24 weeks of treatment, five of this group have completed at least 48 weeks.

RESULTS:

No drug-related serious adverse events, significant laboratory abnormalities, or allergic reactions were observed in the study. The high-dose group experienced a more rapid and larger relative reduction in urinary glycosaminoglycan that was sustained through week 48. Improvements in the 6-minute walk test were observed in all patients with dramatic gains in those walking <100 meters at baseline. Shoulder range of motion improved in all patients at week 48 and joint pain improved in patients with significant pain at baseline.

CONCLUSIONS:

rhASB treatment was well-tolerated and reduced lysosomal storage as evidenced by a dose-dependent reduction in urinary glycosaminoglycan. Clinical responses were present in all patients, but the largest gains occurred in patients with advanced disease receiving high-dose rhASB.

• Authors: Paul Harmatz, Chester B Whitley, Lewis Waber, Ray Pais, Robert Steiner, Barbara Plecko, Paige Kaplan, Julie Simon, Ellen Butensky, John J Hopwood
• Journal: The Journal of pediatrics (J Pediatr) Vol. 144 Issue 5 Pg. 574-80 (May 2004) ISSN: 0022-3476 [Print] United States
• PMID: 15126989 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Recombinant Proteins
• N-Acetylgalactosamine-4-Sulfatase

Topics

• Adolescent
• Child
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Male
• Mucopolysaccharidosis VI (drug therapy)
• N-Acetylgalactosamine-4-Sulfatase (adverse effects, pharmacology, therapeutic use)
• Recombinant Proteins
• Statistics, Nonparametric