ArticleAnnals of clinical and translational neurology2016
Efficacy and ototoxicity of different cyclodextrins in Niemann-Pick C disease.
Article in Annals of clinical and translational neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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Who cites it
52 citing papers in PubMed, 86 citations in OpenAlex.
- Molecular and histological characterizations reveal two distinct senescent microglia populations in Niemann-Pick disease type C mouse model.GeroScience · 2026Article
- Sphingolipid-neutralizing molecular therapy reduces psychosine cytotoxicity in Krabbe disease.iScience · 2026Article
- Plasma Biomarker Profiling of 2-Hydroxypropyl-β-Cyclodextrin (HPβCD) Treatment in an Aged Mouse Model of Ischemic Stroke.International journal of molecular sciences · 2025Article
- Inability of α-cyclodextrins to accommodate cholesterol potentially underlies their lack of efficacy and ototoxicity in Niemann-Pick disease type C treatment.Scientific reports · 2025Article
- Article
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- CAR Macrophages: a promising novel immunotherapy for solid tumors and beyond.Biomarker research · 2024Review
- Enhancing CAR Macrophage Efferocytosis Via Surface Engineered Lipid Nanoparticles Targeting LXR Signaling.Advanced materials (Deerfield Beach, Fla.) · 2024Article
- Differently increased volumes of multiple brain areas inFrontiers in neuroanatomy · 2024Article
- The expanding boundaries of sphingolipid lysosomal storage diseases; insights from Niemann-Pick disease type C.Biochemical Society transactions · 2023Review
- Different solubilizing ability of cyclodextrin derivatives for cholesterol in Niemann-Pick disease type C treatment.Clinical and translational medicine · 2023Article
- Modification of conducting arylidene copolymers by formation of inclusion complexes: synthesis, characterization, and applications as highly corrosion inhibitors for mild steel.BMC chemistry · 2023Article
- Organ Weights inInternational journal of molecular sciences · 2022Article
- Cyclodextrins: Only Pharmaceutical Excipients or Full-Fledged Drug Candidates?Pharmaceutics · 2022Review
- Differential Ganglioside and Cholesterol Depletion by Various Cyclodextrin Derivatives and Their Effect on Synaptosomal Glutamate Release.International journal of molecular sciences · 2022Article
- Impaired Retromer Function in Niemann-Pick Type C Disease Is Dependent on Intracellular Cholesterol Accumulation.International journal of molecular sciences · 2021Article
- Transcriptome of HPβCD-treated Niemann-Pick disease type C1 cells highlights GPNMB as a biomarker for therapeutics.Human molecular genetics · 2021Article
- Cyclodextrins, Natural Compounds, and Plant Bioactives-A Nutritional Perspective.Biomolecules · 2021Review
- Gender-Specific Effects of Two Treatment Strategies in a Mouse Model of Niemann-Pick Disease Type C1.International journal of molecular sciences · 2021Article
- Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
objectiveNiemann-Pick type C (NPC) disease is a fatal, neurodegenerative, lysosomal storage disorder characterized by intracellular accumulation of unesterified cholesterol (UC) and other lipids. While its mechanism of action remains unresolved, administration of 2-hydroxypropyl-β-cyclodextrin (HPβCD) has provided the greatest disease amelioration in animal models but is ototoxic. We evaluated other cyclodextrins (CDs) for treatment outcome and chemical interaction with disease-relevant substrates that could pertain to mechanism.
methodsNPC disease mice treated for 2 weeks with nine different CDs were evaluated for UC, and GM2 and GM3 ganglioside accumulation using immunohisto/cytochemical and biochemical assays. Auditory brainstem responses were determined in wild-type mice administered CDs. CD complexation with UC, gangliosides, and other lipids was quantified.
resultsFour HPβCDs varying in degrees of substitution, including one currently in clinical trial, showed equivalent storage reduction, while other CDs showed significant differences in relative ototoxicity and efficacy, with reductions similar for the brain and liver. Importantly, HPγCD and two sulfobutylether-CDs showed efficacy with reduced ototoxicity. Complexation studies showed: incomplete correlation between CD efficacy and UC solubilization; an inverse correlation for ganglioside complexation; substantial interaction with several relevant lipids; and association between undesirable increases of UC storage in Kupffer cells and UC solubilization.
interpretationCDs other than HPβCD identified here may provide disease amelioration without ototoxicity and merit long-term treatment studies. While direct interactions of CD-UC are thought central to the mechanism of correction, the data show that this does not strictly correlate with complexation ability and suggest interactions with other NPC disease-relevant substrates should be considered.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.