TY - JOUR
T1 - Enzyme replacement therapy in mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)
AU - Harmatz, Paul
AU - Whitley, Chester B.
AU - Waber, Lewis
AU - Pais, Ray
AU - Steiner, Robert
AU - Plecko, Barbara
AU - Kaplan, Paige
AU - Simon, Julie
AU - Butensky, Ellen
AU - Hopwood, John J.
PY - 2004/5
Y1 - 2004/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=1542669902&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1542669902&partnerID=8YFLogxK
U2 - 10.1016/j.jpeds.2004.03.018
DO - 10.1016/j.jpeds.2004.03.018
M3 - Article
C2 - 15126989
AN - SCOPUS:1542669902
SN - 0022-3476
VL - 144
SP - 574
EP - 580
JO - Journal of Pediatrics
JF - Journal of Pediatrics
IS - 5
ER -