TY - JOUR
T1 - Analytical Characterization of Methyl-β-Cyclodextrin for Pharmacological Activity to Reduce Lysosomal Cholesterol Accumulation in Niemann-Pick Disease Type C1 Cells
AU - Li, Rong
AU - Hao, Jon
AU - Fujiwara, Hideji
AU - Xu, Miao
AU - Yang, Shu
AU - Dai, Sheng
AU - Long, Yan
AU - Swaroop, Manju
AU - Li, Changhui
AU - Vu, Mylinh
AU - Marugan, Juan J.
AU - Ory, Daniel S.
AU - Zheng, Wei
N1 - Publisher Copyright:
© 2017 Mary Ann Liebert, Inc.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Methyl-β-cyclodextrin (MβCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease type C1 (NPC1) patient fibroblasts. However, the pharmacological activity of MβCD reported by different laboratories varies. To determine the potential causes of this variation, we analyzed the mass spectrum characteristics, pharmacological activity of three preparations of MβCDs, and the protein expression profiles of NPC1 patient fibroblasts after treatment with different sources of MβCDs. Our data revealed varied mass spectrum profiles and pharmacological activities on the reduction of lysosomal cholesterol accumulation in NPC1 fibroblasts for these three preparations of MβCDs obtained from different batches and different sources. Furthermore, a proteomic analysis showed the differences of these three MβCD preparations on amelioration of dysregulated protein expression levels in NPC1 cells. The results demonstrate the importance of prescreening of different cyclodextrin preparations before use as a therapeutic agent. A combination of mass spectrum analysis, measurement of pharmacological activity, and proteomic profiling provides an effective analytical procedure for characterization of cyclodextrins for therapeutic applications.
AB - Methyl-β-cyclodextrin (MβCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease type C1 (NPC1) patient fibroblasts. However, the pharmacological activity of MβCD reported by different laboratories varies. To determine the potential causes of this variation, we analyzed the mass spectrum characteristics, pharmacological activity of three preparations of MβCDs, and the protein expression profiles of NPC1 patient fibroblasts after treatment with different sources of MβCDs. Our data revealed varied mass spectrum profiles and pharmacological activities on the reduction of lysosomal cholesterol accumulation in NPC1 fibroblasts for these three preparations of MβCDs obtained from different batches and different sources. Furthermore, a proteomic analysis showed the differences of these three MβCD preparations on amelioration of dysregulated protein expression levels in NPC1 cells. The results demonstrate the importance of prescreening of different cyclodextrin preparations before use as a therapeutic agent. A combination of mass spectrum analysis, measurement of pharmacological activity, and proteomic profiling provides an effective analytical procedure for characterization of cyclodextrins for therapeutic applications.
KW - Lysosomal storage disease
KW - mass spectrometry
KW - methyl-b-cyclodextrin
KW - niemann-pick disease type C1
KW - proteomics
UR - http://www.scopus.com/inward/record.url?scp=85021149151&partnerID=8YFLogxK
U2 - 10.1089/adt.2017.774
DO - 10.1089/adt.2017.774
M3 - Article
C2 - 28631941
AN - SCOPUS:85021149151
SN - 1540-658X
VL - 15
SP - 154
EP - 166
JO - Assay and Drug Development Technologies
JF - Assay and Drug Development Technologies
IS - 4
ER -