ArticleBiochimica et biophysica acta. Molecular and cell biology of lipids2019
2-Hydroxypropyl-β-cyclodextrin is the active component in a triple combination formulation for treatment of Niemann-Pick C1 disease.
Article in Biochimica et biophysica acta. Molecular and cell biology of lipids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Advances in research on potential therapeutic approaches for Niemann-Pick C1 disease.Frontiers in pharmacology · 2024Review
- Investigation of 2-Hydroxypropyl-β-Cyclodextrin Treatment in a Neuronal-Like Cell Model of Niemann-Pick Type C Using Quantitative Proteomics.Journal of the American Society for Mass Spectrometry · 2023Article
- Identification of cerebral spinal fluid protein biomarkers in Niemann-Pick disease, type C1.Biomarker research · 2023Article
- Species-specific differences in NPC1 protein trafficking govern therapeutic response in Niemann-Pick type C disease.JCI insight · 2022Article
- Testing the Protective Effects of Sulfobutylether-Βeta-Cyclodextrin (SBECD) and Sugammadex against Chlorpromazine-Induced Acute Toxicity in SH-SY5Y Cell Line and in NMRI Mice.Pharmaceutics · 2022Article
- Improved systemic AAV gene therapy with a neurotrophic capsid in Niemann-Pick disease type C1 mice.Life science alliance · 2021Article
- Inhibition of Histone Deacetylases 1, 2, and 3 Enhances Clearance of Cholesterol Accumulation in Niemann-Pick C1 Fibroblasts.ACS pharmacology & translational science · 2021Article
- Understanding and Treating Niemann-Pick Type C Disease: Models Matter.International journal of molecular sciences · 2020Review
- Correction of Niemann-Pick type C1 trafficking and activity with the histone deacetylase inhibitor valproic acid.The Journal of biological chemistry · 2020Article
- Lipid rafts as a therapeutic target.Journal of lipid research · 2020Review
- Lipid rafts in glial cells: role in neuroinflammation and pain processing.Journal of lipid research · 2020Review
- Individualized management of genetic diversity in Niemann-Pick C1 through modulation of the Hsp70 chaperone system.Human molecular genetics · 2020Article
- Quantitating the epigenetic transformation contributing to cholesterol homeostasis using Gaussian process.Nature communications · 2019Article
Corrections and comments
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Authors and funding
26 authors at 6 institutions in 1 country.
Funding
Abstract
Niemann-Pick type C1 (NPC1) disease is a fatal neurovisceral disease for which there are no FDA approved treatments, though cyclodextrin (HPβCD) slows disease progression in preclinical models and in an early phase clinical trial. Our goal was to evaluate the mechanism of action of a previously described combination-therapy, Triple Combination Formulation (TCF) - comprised of the histone deacetylase inhibitor (HDACi) vorinostat/HPβCD/PEG - shown to prolong survival in Npc1 mice. In these studies, TCF's benefit was attributed to enhanced vorinostat pharmacokinetics (PK). Here, we show that TCF reduced lipid storage, extended lifespan, and preserved neurological function in Npc1 mice. Unexpectedly, substitution of an inactive analog for vorinostat in TCF revealed similar efficacy. We demonstrate that the efficacy of TCF was attributable to enhanced HPβCD PK and independent of NPC1 protein expression. We conclude that although HDACi effectively reduce cholesterol storage in NPC1-deficient cells, HDACi are ineffective in vivo in Npc1 mice.
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Registered trials
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