Multiple approaches of the therapy for lysosomal diseases affected with central nervous system

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Lysosomal diseases were caused by the accumulation of undigested substrates within lysosome. The lysosomal diseases affected in the central nervous system were hard to treat because the recombinant enzyme could not be entered through blood brain barrier. We tried several projects to approach the therapy of these disease, as follows ;1)Express affected enzyme: We tried to construct for the normal galactocerebrosidase to express in large-scale in yeast, however the ratio of expression was not good enough.2)Inhibition of synthetic enzyme of sphingolipid : We realize that cycloserine was confirmed to inhibit production of psychosine. We will check dose dependency for the effect of cycloserine.3)Molecular shaperon : Saposine A was proven to be the activator of galactocerebrosidase and might be shaperon for it. We were succeeded in express saposin A in yeast expression system. Purified saposin A was able to activate β-glucosidase and galactocerebrosidase.4)Activation of affected enzyme: The produced saposin A might be able to bind enzyme and stabilyze them. We are analyzing this effect in vivo.5)Block apoptosis cascade : We check the expression profile of TDAG8 and analyzed the effect of antibody against TDAG8.