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Cited by 21Lysosomal Storage Disorders ResearchBiomedical Research and PathophysiologyGlycogen Storage Diseases and Myoclonus

Analytical Characterization of Methyl-β-Cyclodextrin for Pharmacological Activity to Reduce Lysosomal Cholesterol Accumulation in Niemann-Pick Disease Type C1 Cells

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Li, Rong, Hao, Jon, Fujiwara, Hideji, Xu, Miao, Yang, Shu, Dai, Sheng, Long, Yan, Swaroop, Manju +5 more·2017·ASSAY and Drug Development Technologies
DOI 10.1089/adt.2017.774PMC PMC5510037
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Abstract

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.

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  • A 4-day treatment with 100 μM methyl-β-cyclodextrin (MβCD) mitigates lysosomal cholesterol accumulation in ApoE4 hiPSC-derived astrocytes.

    “We were able to mitigate lysosomal cholesterol accumulation in ApoE4 hiPSC-derived astrocytes with a 4-day treatment of 100 μM methyl-β-cyclodextrin (MβCD)”

    From ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes (2023) · cites this paper as [18]

    The Results section (Fig. 4; page not provided) reports that four days of MβCD treatment reduced cholesterol accumulation in NPC1 patient fibroblasts. It does not report an experiment in ApoE4 hiPSC-derived astrocytes or establish the claimed effect specifically at 100 μM. (LLM, conf=0.88)

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Authors
Li, R., Hao, J., Fujiwara, H., Xu, M., Yang, S., Dai, S., Long, Y., Swaroop, M., Li, C., Vu, M., Marugan, J. J., Ory, D. S., & Zheng, W.
Affiliations
  • National Institutes of Health (US)
  • Poochon Scientific
  • Washington University in St. Louis (US)
  • National Institutes of Health
Corresponding author
Zheng, Wei
ORCID
Venue
ASSAY and Drug Development Technologies
Publisher
SAGE Publications
Published
2017-06
Volume
15
Issue
4
Pages
154-166
ISSN
  • 1540-658X (ISSN-L)
  • 1557-8127
DOI
10.1089/adt.2017.774
PMC
PMC5510037
OpenAlex
W2649171395
Cited by
21
References
0
Citations by year
2025: 2 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 5 · 2017: 2
FWCI
2.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Assay and Drug Development Technologies (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL067773)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK056341)
  • National Institute of Neurological Disorders and Stroke (R01NS081985)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Biomedical Research and Pathophysiology
  • Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
Keywords
methyl-β-cyclodextrin, Niemann-Pick disease type C1, lysosomal cholesterol accumulation, mass spectral characterization, proteomic profiling, pharmaceutical quality control
MeSH terms
Cells, Cultured, Cholesterol, Fibroblasts, Humans, Lysosomes, Mass Spectrometry, Molecular Structure, beta-Cyclodextrins, Niemann-Pick Disease, Type C

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