Replacement therapy in Mucopolysaccharidosis type VI: advantages of early onset of therapy

Mol Genet Metab. 2003 Mar;78(3):163-74. doi: 10.1016/s1096-7192(03)00007-6.


This study evaluates the immunological response following weekly 2h infusions of recombinant human N-acetylgalactosamine 4-sulfatase (rh4S) in Mucopolysaccharidosis VI (MPS VI) cats. The results of three trials (Trial "A": 9 month duration with onset at 3-5 months of age, n = 5; and Trials "B" and "C": 6 month duration starting at birth, n = 9) were compared. No detrimental effects were noted throughout Trials B and C. Temporary hypersensitivity reactions (e.g., vomiting, diarrhoea) occurred in four cats in Trial A and were alleviated by increasing the dose of antihistamine premedication and the duration of infusion. All cats in Trial A developed antibodies to rh4S (range of final titres: 1041-134,931). All cats treated from birth showed negligible titres (range: < 50-598). In vitro inhibition of rh4S activity (up to 47%) was demonstrated with plasma from four cats with elevated titres. Significant reduction of urinary glycosaminoglycan concentration in all cats indicated the ability of rh4S to metabolize stored substrates regardless of the presence of circulating antibodies. Similarly, lysosomal storage in reticuloendothelial cells and fibroblasts of kidney interstistium, dura and skin was reduced in all cats irrespective of their antibody titre although cats with elevated titre had less beneficial effect on cardiovascular tissues (aorta smooth muscle cells, heart valve fibroblasts). Overall improvement in the disease condition (at physical, neurological, and skeletal levels) was most pronounced for cats treated from birth compared with cats treated at a later age.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Autopsy
  • Bone and Bones / abnormalities
  • Bone and Bones / pathology
  • Cats
  • Complement Hemolytic Activity Assay
  • Cyproheptadine / therapeutic use
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Glycosaminoglycans / urine
  • Humans
  • Hypersensitivity / drug therapy
  • Lysosomes / pathology
  • Mucopolysaccharidosis VI / immunology*
  • Mucopolysaccharidosis VI / pathology
  • Mucopolysaccharidosis VI / therapy*
  • N-Acetylgalactosamine-4-Sulfatase / adverse effects
  • N-Acetylgalactosamine-4-Sulfatase / metabolism
  • N-Acetylgalactosamine-4-Sulfatase / pharmacology*
  • N-Acetylgalactosamine-4-Sulfatase / therapeutic use*
  • Organ Specificity
  • Time Factors
  • Treatment Outcome


  • Glycosaminoglycans
  • Cyproheptadine
  • N-Acetylgalactosamine-4-Sulfatase