Delivery of active hexosaminidase across the blood-brain barrier in rats.

The ability to deliver enzymatically active human hexosaminidase A across the blood-brain barrier and into brain cells of the normal rat was examined. Following osmotic blood-brain barrier modification in the rat, intraarterially administered human hexosaminidase A and B were shown to cross the barrier and enter brain cells. Subcellular fractionation studies demonstrated that most of the human enzyme delivered across the barrier was functionally active and appeared to be inside a subcellular organelle. These studies provide evidence that blood-brain barrier modification permits delivery of functionally active hexosaminidase A into subcellular organelles consistent with that known to be the appropriate site of physiologic activity.