Abstract. Here we hypothesized that the water-soluble lysosomal enzymes may cross the blood–brain-barrier and reach the brain using the mechanism of unspecific fluid-phase endocytosis.n fact, there has been increasing evidence that when high serum levels of lysosomal enzymes are achieved, either by GT or ERT, a small fraction of the enzyme is able to cross the BBB by mechanisms not clearly understood [6] , [7] and [8] . Table 1.