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


METHODS
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.
Harmatz
Paul
P
Pediatric Clinical Research Center, Children's Hospital & Research Center at Oakland, California 94606, USA. Pharmatz@mail.cho.org
Whitley
Chester B
CB
Waber
Lewis
L
Pais
Ray
R
Steiner
Robert
R
Plecko
Barbara
B
Kaplan
Paige
P
Simon
Julie
J
Butensky
Ellen
E
Hopwood
John J
JJ
D000293:Adolescent; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009087:Mucopolysaccharidosis VI / Q000188:drug therapy*; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins; D018709:Statistics, Nonparametric
D011994:Recombinant Proteins; D020051:N-Acetylgalactosamine-4-Sulfatase