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Therapeutic Effects of Dipolar Aprotic Substances on Niemann‐Pick Cells
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AbstractDimethylsulfoxide (Me2SO) increased acid sphingomyelinase activity in cultured skin fibroblasts (Sakuragawa N et al., Biochem Biophy Res Comm 1985; 126: 756–762). Various drugs were examined to find related compounds showing the same phenomenon as Me2 SO, including other dipolar aprotic substances, various inhibitors of DNA and RNA synthesis, phorbol esters, vitamin E and its derivatives and other miscellaneous agents. Several dipolar aprotic substances, such as Me2SO, dimethylacetamide, tetramethylurea and hexa‐methylene‐bisacetamide, increased the acid and Mg‐independent neutral sphingomyelinase activity in human cultured skin fibroblasts. These dipolar aprotic substances also increased acid and Mg‐independent neutral sphingomyelinase activities in Niemann‐Pick cells, type C, to 300 to 700% of those of untreated controls, repairing their enzyme deficiency. Other lysosomal hydrolases increased to a slightly lesser extent than sphingomyelinase. Dipolar aprotic substances could be used as therapeutic drugs for Niemann‐Pick disease, type C.
Title: Therapeutic Effects of Dipolar Aprotic Substances on Niemann‐Pick Cells
Description:
AbstractDimethylsulfoxide (Me2SO) increased acid sphingomyelinase activity in cultured skin fibroblasts (Sakuragawa N et al.
, Biochem Biophy Res Comm 1985; 126: 756–762).
Various drugs were examined to find related compounds showing the same phenomenon as Me2 SO, including other dipolar aprotic substances, various inhibitors of DNA and RNA synthesis, phorbol esters, vitamin E and its derivatives and other miscellaneous agents.
Several dipolar aprotic substances, such as Me2SO, dimethylacetamide, tetramethylurea and hexa‐methylene‐bisacetamide, increased the acid and Mg‐independent neutral sphingomyelinase activity in human cultured skin fibroblasts.
These dipolar aprotic substances also increased acid and Mg‐independent neutral sphingomyelinase activities in Niemann‐Pick cells, type C, to 300 to 700% of those of untreated controls, repairing their enzyme deficiency.
Other lysosomal hydrolases increased to a slightly lesser extent than sphingomyelinase.
Dipolar aprotic substances could be used as therapeutic drugs for Niemann‐Pick disease, type C.
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