Attenuation of ganglioside GM1 accumulation in the brain of GM1 gangliosidosis mice by neonatal intravenous gene transfer.

A single intravenous injection with 4 x 10(7) PFU of recombinant adenovirus encoding mouse beta-galactosidase cDNA to newborn mice provided widespread increases of beta-galactosidase activity, and attenuated the development of the disease including the brain at least for 60 days. The beta-galactosidase activity showed 2-4 times as high a normal activity in the liver and lung, and 50 times in the heart. In the brain, while the activity was only 10-20% of normal, the efficacy of the treatment was distinct. At the 30th day after the injection, significant attenuation of ganglioside GM1 accumulation in the cerebrum was shown in three out of seven mice. At the 60th day after the injection, the amount of ganglioside GM1 was above the normal range in all treated mice, which was speculated to be the result of reaccumulation. However, the values were still definitely lower in most of the treated mice than those in untreated mice. In the histopathological study, X-gal-positive cells, which showed the expression of exogenous beta-galactosidase gene, were observed in the brain. It is noteworthy that neonatal administration via blood vessels provided access to the central nervous system because of the incompletely formed blood-brain barrier.