Representative Images of NPC1 Mutant Cells After Treatment with Various Compounds.

<p>GM03123 NPC1 mutant fibroblasts were treated with various drugs and combinations of drugs with 200 µM β-cyclodextrin for 48 hours, after which they were fixed, filipin stained, and imaged under UV excitation as described in Materials and Methods. Images are shown after contrast adjustment but prior to threshold application. The concentrations used in each displayed image for vorinostat, panobinostat, β-cyclodextrin, rapamycin, decitabine, chloroquine, and chlorpromazine were 10 µM, 75 nM, 200 µM, 7.5 nM, 0.625 µM, 50 µM, and 20 µM, respectively. Reduced cholesterol levels, as evidenced through decreased filipin fluorescence relative to solvent controls, are clearly observed in the vorinostat, panobinostat, β-cyclodextrin, and rapamycin treated cells. Further diminished fluorescence is observed in cells treated with both the drug and β-cyclodextrin (Drug + β-CD). No visibly obvious decrease in fluorescence is observed between cells treated with decitabine, chloroquine, or chlorpromazine, and their respective controls.