Differential neurologic outcome of gene therapy and HCT. (A) Repeated open-field test was performed on treated and control mice 6 months after the transplantation. Horizontal activity of MPS I (n = 20), HCT (n = 18), GT (n = 17), and WT (n = 14) mice is reported as a percentage (%) of change between the 1st and the 3rd days. (B) GT mice were divided into 2 groups according to the IDUA activity measured on their brain. The percentage change in horizontal activity between the first and third trials is shown for animals having brain IDUA activity lower (<, n = 8) or higher (>, n = 9) than 20 nmol/mg/h (20 nmol/mg/h is the average activity value measured on the brain of the entire population of GT mice). Mean ± SD are shown; *P < .05; **P < .01; ***P < .001 with 1-way ANOVA in panel A and Student t test in panel B. (C) Purkinje cell frequency (expressed as percentage of the cells counted in WT mice; dense area) and percentage of degenerated Purkinje cells among the total cells (scattered area) in cerebellum slices from affected, WT-, HCT-, and GT-treated mice are shown (see “Methods” for details). Mean ± SD values are shown; n ≥ 4 representative mice analyzed per group (≥ 3 representative sections per mouse). (D) Representative semithin section images from the Purkinje cell layer of treated and control mice, as indicated. The pictures show degenerating Purkinje cells, which, besides accumulating GAGs, display shrunken cell bodies and darkly stained nuclei (arrows, “gl” marks granular layer), in mock-transplanted MPS I mice; in HCT mice, residual storage and Purkinje cell degeneration were seen, whereas in the GT-treated mice we observed a complete rescue of the pathologic phenotype. Magnification ×100 in the images from the top row, ×200 in the bottom row.