Effects of intracerebroventricular administration of 2-hydroxypropyl-β-cyclodextrin in a patient with Niemann–Pick Type C disease

Matsuo, Muneaki; Shraishi, Koki; Wada, Koh; Ishitsuka, Yoichi; Doi, Hirohito; Maeda, Miyuki; Mizoguchi, Tatsuhiro; Eto, Junya; Mochinaga, Sakiko; Arima, Hisatomi; Irie, Tetsumi

doi:10.1016/j.ymgmr.2014.08.004

Cited by 48 publications

(38 citation statements)

References 16 publications

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“…Since then, three additional NP-C cases treated by IT HPBCD have been reported, one in a 2-year-old girl,4 another in a 6-year-old girl,5 and the last in a 12-year-old boy 6. In all cases, the disease stabilised during the time patients were receiving HPBCD.…”

Section: Investigationsmentioning

confidence: 98%

Intrathecal cyclodextrin in the treatment of Niemann-Pick disease type C

et al. 2016

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CaseA child with Niemann-Pick disease type C was started on miglustat therapy at the age of 2 years. Intrathecal administration of hydroxypropyl-β-cyclodextrin was added 5 months later. The initial dose of 175 mg was gradually increased over the first 6 months to reach 325 mg. The drug was administered every 15 days, and the patient received 43 doses. A slight delay in progression of the disease was seen during the first year of intrathecal hydroxypropyl-β-cyclodextrin. However, additional symptoms have emerged since that time, suggesting a lack of effectiveness of the drug. Our patient has shown no drug-related adverse events.ConclusionsIntrathecal hydroxypropyl-β-cyclodextrin therapy is safe, but its efficacy seems questionable in a patient with the severe infantile form of Niemann-Pick disease type C.

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Section: Investigationsmentioning

confidence: 98%

Intrathecal cyclodextrin in the treatment of Niemann-Pick disease type C

et al. 2016

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“…Recently, various bioactivities of CyDs have been demonstrated, and CyDs have been used as active pharmaceutical ingredients (APIs) against Niemann-Pick disease type C (NPC), [62][63][64][65][66][67][68][69][70][71][72][73][74][75][76] leukemia, 77) hyperlipidemia, 78) Alzheimer's disease, [79][80][81][82][83][84] cerebral ischemic injury, 85) atherosclerosis, 86) diabetic kidney disease, 87) chronic renal failure, 88) AIDS, 89,90) influenza, 91) peripheral artery disease, 92) sterility, [93][94][95] solid cancers, [96][97][98][99][100][101] bacterial growth, 102) α-synucleinopathy, 103) GM1-gangliosidosis, 104) septic shock, [105][106][107] hypervitaminosis, 108) and transthyretin-related familial amyloidotic polyneuropathy (FAP) …”

Section: Cyclodextrin-based Supramolecular Pharmacology and Drug Discmentioning

confidence: 99%

Supramolecular Pharmaceutical Sciences: A Novel Concept Combining Pharmaceutical Sciences and Supramolecular Chemistry with a Focus on Cyclodextrin-Based Supermolecules

et al. 2018

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Supramolecular chemistry is an extremely useful and important domain for understanding pharmaceutical sciences because various physiological reactions and drug activities are based on supramolecular chemistry. However, it is not a major domain in the pharmaceutical field. In this review, we propose a new concept in pharmaceutical sciences termed "supramolecular pharmaceutical sciences," which combines pharmaceutical sciences and supramolecular chemistry. This concept could be useful for developing new ideas, methods, hypotheses, strategies, materials, and mechanisms in pharmaceutical sciences. Herein, we focus on cyclodextrin (CyD)-based supermolecules, because CyDs have been used not only as pharmaceutical excipients or active pharmaceutical ingredients but also as components of supermolecules.

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“…Two reported cases of Japanese NPD-C patients diagnosed at 2 months and 13 years were initially treated at 4 and 14 years old with the IV "Oakland protocol", with doses from 80 mg to 2500 mg/kg/three or two times a week, respectively [37,38]. These were the first published cases of VTS-270 use in NPD-C.…”

Section: Experience In Humans: Efficacy Of the Intravenous Administramentioning

confidence: 99%

“…Furthermore, repeated fever with transient diffuse pulmonary cloudiness episodes were observed, an AE probably related to HP-β-CD IV infusion. After 2 years of IV therapy, IT first and later ICV administrations were combined with IV infusions [38]. The combined therapy obtained objective benefits in EEG, PET and magnetic resonance spectroscopy (MRS), and CSF T-tau level reduction.…”

Section: Experience In Humans: Efficacy Of the Intravenous Administramentioning

confidence: 99%

“…Despite the positive results observed in the compassionate use of IV HP-β-CD [26,27,[32][33][34][35][36][37][38][39], there is no clear evidence to date that IV route has a clinical benefit in CNS symptoms of NPD-C in humans. Most of the reports with neurological improvements combined the use of IV and IT/ICV administrations, making it impossible to demonstrate that these benefits were exclusively associated to IV and not IT/ICV.…”

Section: Experience In Humans: Efficacy Of the Intravenous Administramentioning

confidence: 99%

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Use of 2-Hydroxypropyl-Beta-Cyclodextrin for Niemann-Pick Type C Disease

Megías‐Vericat¹,

Company-Albir²,

García-Robles³

et al. 2018

Cyclodextrin - A Versatile Ingredient

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Niemann-Pick disease type C (NPD-C) is a rare neurodegenerative disorder characterized by a lysosomal storage disorder. Treatment has been supportive and symptomatic. In animal studies, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) showed a significant decrease in cerebellar damage, neurological progression, and higher lifespan. Based on these results, HP-β-CD has been tested in NPD-C patients for last 8 years. The first compassionate uses of intravenous HP-β-CD obtained a limited improvement in neurological symptoms, probably associated to the non-permeation of the blood-brain barrier. The change or combination with intrathecal administrations of HP-β-CD achieved higher benefits, especially improvement or stabilization of NPD-C progression. Biomarkers of neurological cholesterol homeostasis are being investigated in order to quantify the response of HP-β-CD treatment. The results of a clinical trial recently published have reproduced the slowing of NPD-C progression in 14 patients treated with a dose-escalation protocol of HP-β-CD intrathecal monthly infusions, with respect to a historical comparison cohort. The safety profile of this therapy is acceptable, being the loss of hearing as the most frequent adverse event. However, some severe toxicities have been reported in relation with HP-β-CD, including chemical meningitis and fever. The short experience with HP-β-CD suggested that it could be effective in the management of NPD-C.

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Effects of intracerebroventricular administration of 2-hydroxypropyl-β-cyclodextrin in a patient with Niemann–Pick Type C disease

Cited by 48 publications

References 16 publications

Intrathecal cyclodextrin in the treatment of Niemann-Pick disease type C

Intrathecal cyclodextrin in the treatment of Niemann-Pick disease type C

Supramolecular Pharmaceutical Sciences: A Novel Concept Combining Pharmaceutical Sciences and Supramolecular Chemistry with a Focus on Cyclodextrin-Based Supermolecules

Use of 2-Hydroxypropyl-Beta-Cyclodextrin for Niemann-Pick Type C Disease

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