Treatment of
mucopolysaccharidosis type VII (MPS VII) mice with recombinant mouse
beta-glucuronidase injections has been shown to deliver
enzyme to most tissues and to reduce lysosomal storage during the first 6 wk of life. Here we determine the effect of
enzyme therapy limited to the first 6 wk of life on survival and growth and follow the subsequent accumulation of lysosomal storage after
beta-glucuronidase treatment is discontinued. MPS VII mice received 28,000 U of
beta-glucuronidase i.v. at weekly intervals from birth to 6 wk of life and were killed at intervals up to 1 y after the last injection. By 29 d after the last
enzyme injection, lysosomal storage in bone was no different in amount than that seen in untreated MPS VII mice. By 85 d, the fixed tissue macrophage system, meninges, and brain glia had also accumulated storage comparable to that seen in untreated controls. One year
after treatment, lysosomal storage was similar to that of untreated MPS VII mice in all sites except cortical neurons, where there was still a slight reduction. All treated mice that were not killed earlier, lived longer, were larger, and had milder facial and skeletal
deformities than untreated MPS VII mice. These data show that
enzyme replacement therapy in MPS VII mice during the first 6 wk of life improve survival and growth.
After treatment is discontinued, storage accumulates slowly in the brain and more rapidly in the fixed tissue macrophage system. Whether
therapy continued later in life can further improve survival and growth remains to be established.