BACKGROUND: Wolman disease (WD) is a rare lysosomal storage disorder that is 
caused by mutations in the LIPA gene encoding lysosomal acid lipase (LAL). 
Deficiency in LAL function causes accumulation of cholesteryl esters and 
triglycerides in lysosomes. Fatality usually occurs within the first year of 
life. While an enzyme replacement therapy has recently become available, there 
is currently no small-molecule drug treatment for WD.
RESULTS: We have generated induced pluripotent stem cells (iPSCs) from two WD 
patient dermal fibroblast lines and subsequently differentiated them into neural 
stem cells (NSCs). The WD NSCs exhibited the hallmark disease phenotypes of 
neutral lipid accumulation, severely deficient LAL activity, and increased 
LysoTracker dye staining. Enzyme replacement treatment dramatically reduced the 
WD phenotype in these cells. In addition, δ-tocopherol (DT) and 
hydroxypropyl-beta-cyclodextrin (HPBCD) significantly reduced lysosomal size in 
WD NSCs, and an enhanced effect was observed in DT/HPBCD combination therapy.
CONCLUSION: The results demonstrate that these WD NSCs are valid cell-based 
disease models with characteristic disease phenotypes that can be used to 
evaluate drug efficacy and screen compounds. DT and HPBCD both reduce 
LysoTracker dye staining in WD cells. The cells may be used to further dissect 
the pathology of WD, evaluate compound efficacy, and serve as a platform for 
high-throughput drug screening to identify new compounds for therapeutic 
development.