Fig. 1.

IDUA Activity in plasma and tissues after intravenous administration of AAV9 and AAVrh10 vectors delivering the IDUA gene. (A) Enzyme activity in plasma. Blood was collected at 1 to 2 week intervals and plasma was assayed for IDUA activity. High and sustained levels of IDUA activity were seen in plasma from animals treated with bith serotypes (n = 5; each serotype). The level of plasma IDUA activity in normal heterozygotes (n = 4) is indicated by a dashed line and ranges from 0.5–2 nmoles/hr/ml. Enzyme activity in plasma from MPS I animals (n= 4) was undetectable (<0.05 nmoles/hr/ml). Bars represent means +/− SD. (B) IDUA enzyme activity in brain No CR.

Brains were micro-dissected and extracts assayed for IDUA enzyme activity. There was widespread IDUA activity in the brains of treated animals (n = 5) compared to wild type animals. Enzyme activity found in normal heterozygotes (n = 4) is indicated by the dashed line, and ranges from 1 to 15 nmoles/h/mg in the brain. Enzyme activity was not detected in untreated MPS I animals (<0.05 nmoles/h/mg, n = 4). Mean +/− SD values are represented by bold horizontal lines and light vertical lines respectively. HP, hippocampus; CB, cerebellum; CTX, cortex; S, striatum; OB, olfactory bulb; THAL, thalamus; SC, spinal cord. No CR.

(C) IDUA enzyme activity in peripheral organs. Levels of IDUA activity were extremely high in peripheral organs of mice from treated animals. The range of enzyme activities found in normal heterozygotes is indicated by the dashed line, and ranges from 1-15 nmoles/hr/mg. Enzyme activity was not detected in untreated animals (<0.05 nmoles/hr/mg).

Mean +/− SD values are represented by bold horizontal lines and light vertical lines respectively.