Monitoring dose response of enzyme replacement therapy in feline mucopolysaccharidosis type VI by tandem mass spectrometry.

Mucopolysaccharidosis type VI is an inherited disorder of glycosaminoglycan metabolism characterized by organomegaly, corneal clouding, and skeletal dysplasia. Recent developments in the use of tandem mass spectrometry to measure sulfated mono- and disaccharides have enabled us to perform noninvasive, biochemical monitoring during therapy regimes in mucopolysaccharidosis type VI cats in addition to established methods of disease evaluation. In this study, mucopolysaccharidosis type VI animals were given high-dose (20 mg/kg) enzyme replacement therapy for the first month after birth followed by low doses (1 mg/kg) for a further 2 mo and were compared with animals maintained on 1 mg/kg enzyme replacement therapy for 3 mo. A sulfated monosaccharide (N-acetylhexosamine) and a sulfated disaccharide (N-acetylhexosamine-uronic acid) were elevated in MPS VI cat urine and blood. These markers showed a clear discrimination between the treatment groups during the first 4 wk of therapy: values in the high-dose group were close to normal whereas those in the low-dose group were only slightly lower than the untreated mucopolysaccharidosis type VI cats. However, within 2 mo of cessation of the high-dose therapy there was minimal difference in the oligosaccharide levels, with both groups lying between the untreated and unaffected cats. At the completion of the trial, subjective minor improvement was noted in overall physical disease features and also in lysosomal vacuolation in tissues from animals on the initial high-dose enzyme replacement therapy compared to the low-dose therapy animals. Initial high-dose therapy reduced storage load in the animals but had no lasting clinical benefit over continuous low-dose therapy.