***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Aim : Mucopolysaccharidosis VI ( Maroteaux – Lamy syndrome ) is a lysosomal storage disease caused by a deficiency of the enzyme N‐acetylgalactosamine 4‐sulphatase ( ASB ) . Enzyme replacement therapy with recombinant human ASB ( rhASB ) has been studied in a r and omized , double‐blind , two‐dose ( 0.2 and 1.0 mg/kg/week ) phase I/II study ( n=7 ) followed by an open‐label single dose ( 1.0 mg/kg/week ) extension study . We report the pharmacokinetic profile of rhASB and the impact of antibody development . Methods : Pharmacokinetic analysis was performed at weeks 1 , 2 , 12 , 24 , 83 , 84 and 96 . Infusions were administered over 4 hours using a ramp‐up protocol . Plasma ASB and rhASB antibody concentrations and urine glycosaminoglycan ( GAG ) concentrations were determined . Results : The area under the plasma concentration – time curve ( AUC0−t ) for the high‐dose group increased from week 1 to week 2 , but remained unchanged at weeks 12 and 24 . A large difference in mean AUC0−t was observed between the low‐ and high‐dose groups . Pharmacokinetic results at weeks 83 , 84 and 96 were similar to those at week 24 . Six patients developed antibodies to rhASB . One patient developed high antibody levels in combination with a high ASB concentration , while a second patient also developed high antibody levels with undetectable ASB concentrations . Antibodies from the second patient blocked detection of ASB . By week 72 , antibody levels had decreased in all patients . The high‐dose rhASB produced a more rapid and greater percentage reduction in urinary GAG concentrations than the lower dose ( 70 % versus 55 % at 24 weeks ) . Antibody levels did not appear to influence urinary GAG concentrations 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 , r and omized , two-dose , double-blind study . Patients were r and omized 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 evidence d 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 Objective . Mucopolysaccharidosis VI ( MPS VI ; Maroteaux-Lamy syndrome ) is a lysosomal storage disease caused by a deficiency of the enzyme N-acetylgalactosamine 4-sulfatase ( ASB ) . This enzyme deficiency leads to a progressive disorder with multiple tissue and organ involvement . The disease is rare and is heterogeneous in its clinical presentation and progression . A potential treatment for this disease exists in the form of enzyme-replacement therapy ( ERT ) with recombinant human ASB ( rhASB ) , and a phase 1/2 r and omized , double-blind , 2-dose ( 0.2 and 1 mg/kg ) study in 6 patients showed the treatment at 48 weeks to be well tolerated . Greater biochemical efficacy based on a urine glycosaminoglycan occurred in the high-dose ( 1 mg/kg ) group , and functional improvement seemed greater in patients in the high-dose group with rapidly advancing disease . On the basis of the phase 1/2 results , a phase 2 , open-label study in patients with rapidly advancing disease was initiated primarily to evaluate efficacy variables that measure endurance , mobility , and joint function in a larger group of patients . Methods . This was an open-label , multinational study of 10 MPS VI patients who received 48 weekly intravenous treatments with 1.0 mg/kg rhASB  and had assessment s of biochemical and clinical responses at regular intervals . Results . After 24 weeks of treatment , each patient on average experienced a 155-m ( 98 % ) improvement in the 12-minute walk , a 64-m ( 62 % ) improvement at the 6-minute time point of the 12-minute walk , and a 48-stair ( 110 % ) gain in the 3-minute stair climb versus the baseline mean values . Additional improvements after 48 weeks of treatment were observed , including mean values of 211 m ( 138 % ) in the 12-minute walk , 75 m ( 80 % ) at the 6-minute time point of the 12-minute walk , and 61-stair ( 147 % ) gain in the 3-minute stair climb versus the baseline mean values . Joint Pain and Stiffness Question naire scores improved by at least 50 % by week 24 and were maintained at week 48 , whereas there were only small improvements in active shoulder range of motion ( < 10 ° ) and in the time taken to st and , walk , and turn starting from a seated position ( Exp and ed Timed Get-Up and Go test ) . Improvement in pulmonary function based on forced vital capacity and forced expiratory volume at 1 minute in the absence of growth was observed in 3 of 6 patients , and the observed gains occurred in the 24- to 48-week treatment interval . A mean decrease of 76 % in urinary excretion of glycosaminoglycans indicated that a satisfactory biochemical response was achieved and the ERT was well tolerated . Conclusions . The results suggest that a 12-minute walk extends the dynamic range of the conventional 6-minute walk and , along with the 3-minute stair climb , provide a robust approach to documenting the improvement in endurance in MPS VI patients who undergo ERT with rhASB UNLABELLED The objective of this study was to evaluate the long-term clinical benefits and safety of recombinant human arylsulfatase B ( rhASB ) treatment of mucopolysaccharidosis type VI ( MPS VI : Maroteaux-Lamy syndrome ) , a lysosomal storage disease . Fifty-six patients derived from 3 clinical studies were followed in open-label extension studies for a total period of 97 - 260 Weeks . All patients received weekly infusions of rhASB at 1 mg/kg . Efficacy was evaluated by ( 1 ) distance walked in a 12-minute walk test ( 12MWT ) or 6-minute walk test ( 6MWT ) , ( 2 ) stairs climbed in the 3-minute stair climb ( 3MSC ) , and ( 3 ) reduction in urinary glycosaminoglycans ( GAG ) . Safety was evaluated by compliance , adverse event ( AE ) reporting and adherence to treatment . RESULTS A significant reduction in urinary GAG ( 71 - 79 % ) was sustained . For the 12MWT , subjects in Phase 2 showed improvement of 255+/-191 m ( mean+/-SD ) at Week 144 ; those in Phase 3 Extension demonstrated improvement from study baseline of 183+/-26 m ( mean+/- SE ) in the rhASB/rhASB group at Week 96 and from treatment baseline ( Week 24 ) of 117+/-25 m in the placebo/rhASB group . The Phase 1/2 6MWT and the 3MSC from Phase 2 and 3 also showed sustained improvements through the final study measurements . Compliance was 98 % overall . Only 560 of 4121 reported AEs ( 14 % ) were related to treatment with only 10 of 560 ( 2 % ) described as severe . CONCLUSION rhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile OBJECTIVE The objective of this Phase 3 study was to confirm the efficacy and safety of recombinant human arylsulfatase B ( rhASB ) treatment of mucopolysaccharidosis type VI ( MPS VI ; Maroteaux-Lamy syndrome ) , a rare , fatal lysosomal storage disease with no effective treatment . STUDY DESIGN Thirty-nine patients with MPS VI were evaluated in a r and omized , double-blind , placebo-controlled , multicenter , multinational study for 24 weeks . The primary efficacy variable was the distance walked in a 12-minute walk test ( 12MWT ) , whereas the secondary efficacy variables were the number of stairs climbed in a 3-minute stair climb ( 3MSC ) and the level of urinary glycosaminoglycan ( GAG ) excretion . All patients received drug in an open-label extension period for an additional 24 weeks . RESULTS After 24 weeks , patients receiving rhASB walked on average 92 meters ( m ) more in the 12MWT ( p=.025 ) and 5.7 stairs per minute more 3MSC ( p=.053 ) than patients receiving placebo . Continued improvement was observed during the extension study . Urinary GAG declined by -227+/-18 microg/mg more with rhASB than placebo ( p<.001 ) . Infusions were generally safe and well tolerated . Patients exposed to drug experienced positive clinical benefit despite the presence of antibody to the protein . CONCLUSION rhASB significantly improves endurance , reduces GAG , and has an acceptable safety profile 
    Output:
    
Long-term follow-up will be required to ascertain full clinical benefit , on both event-free survival and quality of life measures .