Intravenous 2-hydroxypropyl-β-cyclodextrin (Trappsol® Cyclo™) demonstrates biological activity and impacts cholesterol metabolism in the central nervous system and peripheral tissues in adult subjects with Niemann-Pick Disease Type C1: Results of a phase 1 trial
Niemann-Pick Disease Type C1 (NPC1) is a disorder of intracellular cholesterol and lipid trafficking that leads to the accumulation of cholesterol and lipids in the late endosomal/lysosomal compartment, resulting in systemic manifestations (including hepatosplenomegaly and lung infiltration) and neu...
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| Published in | Molecular genetics and metabolism Vol. 137; no. 4; pp. 309 - 319 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
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United States
Elsevier Inc
01.12.2022
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| Online Access | Get full text |
| ISSN | 1096-7192 1096-7206 1096-7206 |
| DOI | 10.1016/j.ymgme.2022.10.004 |
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| Abstract | Niemann-Pick Disease Type C1 (NPC1) is a disorder of intracellular cholesterol and lipid trafficking that leads to the accumulation of cholesterol and lipids in the late endosomal/lysosomal compartment, resulting in systemic manifestations (including hepatosplenomegaly and lung infiltration) and neurodegeneration. Preclinical studies have demonstrated that systemically administered 2-hydroxypropyl-β-cyclodextrin (HPβCD; Trappsol® Cyclo™) restores cholesterol metabolism and homeostasis in peripheral organs and tissues and in the central nervous system (CNS). Here, we assessed the safety, pharmacokinetics, and pharmacodynamics of HPβCD in peripheral tissues and the CNS in adult subjects with NPC1.
A Phase 1, randomized, double-blind, parallel group study enrolled 13 subjects with NPC1 who received either 1500 mg/kg or 2500 mg/kg HPβCD intravenously every 2 weeks for a total of 7 doses (14 weeks). Subjects were 18 years or older, with a confirmed diagnosis of NPC1 and evidence of systemic involvement on clinical assessment. Pharmacokinetic evaluations in plasma and cerebrospinal fluid (CSF) were performed at the first and seventh infusions. Pharmacodynamic assessments included biomarkers of systemic cholesterol synthesis (serum lathosterol) and degradation (serum 4β-hydroxycholesterol), secondary sphingomyelin storage (plasma lysosphingomyelin-509, now more accurately referred to as N-palmitoyl-O-phosphocholineserine [PPCS]), and CNS-specific biomarkers of neurodegeneration (CSF total Tau) and cholesterol metabolism (serum 24(S)-hydroxycholesterol [24(S)-HC]). Safety monitoring included assessments of liver and kidney function, infusion related adverse events, and hearing evaluations.
Ten subjects completed the study, with 6 at the 1500 mg/kg dose and 4 at the 2500 mg/kg dose. One subject withdrew following the first infusion after experiencing hypersensitivity pneumonitis, and 2 subjects withdrew after meeting a stopping rule related to hearing loss. Overall, HPβCD had an acceptable safety profile. The observed pharmacokinetic profile of HPβCD was similar following the first and seventh infusions, with a plasma half-life of 2 h, a maximum concentration reached at 6 to 8 h, and no evidence of accumulation. Serum biomarkers of cholesterol metabolism showed reduced synthesis and increased degradation. Compared to Baseline, filipin staining of liver tissue showed significant reductions of trapped unesterified cholesterol at both dose levels at Week 14. Plasma PPCS levels were also reduced. HPβCD was detected at low concentrations in the CSF (maximum, 33 μM) at both dose levels and persisted longer in CSF than in plasma. Total Tau levels in CSF decreased in most subjects. Serum levels of 24(S)-HC, a cholesterol metabolite from the CNS that is exported across the blood-brain barrier and into the circulation, decreased after both the first and seventh doses. Hence, pharmacodynamic assessments in both peripheral and CNS-related tissue show target engagement. While not the aim of the study, subjects reported favorable impacts on their quality of life.
The plasma pharmacokinetics and pharmacodynamics of HPβCD administered at two intravenous dose levels to subjects with NPC1 were comparable to those observed in preclinical models. HPβCD cleared cholesterol from the liver and improved peripheral biomarkers of cholesterol homeostasis. At low CSF concentrations, HPβCD appeared to be pharmacologically active in the CNS based on the increased efflux of 24(S)-HC and reduction in CSF total Tau, a biomarker of CNS neurodegeneration. These data support the initiation of longer-term clinical trials to evaluate the safety and efficacy of intravenous HPβCD in subjects with NPC1. (ClinicalTrials.gov numbers: present trial, NCT02939547; open-label extension of the present trial, NCT 03893071; global pivotal trial, NCT04860960). |
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| AbstractList | Niemann-Pick Disease Type C1 (NPC1) is a disorder of intracellular cholesterol and lipid trafficking that leads to the accumulation of cholesterol and lipids in the late endosomal/lysosomal compartment, resulting in systemic manifestations (including hepatosplenomegaly and lung infiltration) and neurodegeneration. Preclinical studies have demonstrated that systemically administered 2-hydroxypropyl-β-cyclodextrin (HPβCD; Trappsol® Cyclo™) restores cholesterol metabolism and homeostasis in peripheral organs and tissues and in the central nervous system (CNS). Here, we assessed the safety, pharmacokinetics, and pharmacodynamics of HPβCD in peripheral tissues and the CNS in adult subjects with NPC1.
A Phase 1, randomized, double-blind, parallel group study enrolled 13 subjects with NPC1 who received either 1500 mg/kg or 2500 mg/kg HPβCD intravenously every 2 weeks for a total of 7 doses (14 weeks). Subjects were 18 years or older, with a confirmed diagnosis of NPC1 and evidence of systemic involvement on clinical assessment. Pharmacokinetic evaluations in plasma and cerebrospinal fluid (CSF) were performed at the first and seventh infusions. Pharmacodynamic assessments included biomarkers of systemic cholesterol synthesis (serum lathosterol) and degradation (serum 4β-hydroxycholesterol), secondary sphingomyelin storage (plasma lysosphingomyelin-509, now more accurately referred to as N-palmitoyl-O-phosphocholineserine [PPCS]), and CNS-specific biomarkers of neurodegeneration (CSF total Tau) and cholesterol metabolism (serum 24(S)-hydroxycholesterol [24(S)-HC]). Safety monitoring included assessments of liver and kidney function, infusion related adverse events, and hearing evaluations.
Ten subjects completed the study, with 6 at the 1500 mg/kg dose and 4 at the 2500 mg/kg dose. One subject withdrew following the first infusion after experiencing hypersensitivity pneumonitis, and 2 subjects withdrew after meeting a stopping rule related to hearing loss. Overall, HPβCD had an acceptable safety profile. The observed pharmacokinetic profile of HPβCD was similar following the first and seventh infusions, with a plasma half-life of 2 h, a maximum concentration reached at 6 to 8 h, and no evidence of accumulation. Serum biomarkers of cholesterol metabolism showed reduced synthesis and increased degradation. Compared to Baseline, filipin staining of liver tissue showed significant reductions of trapped unesterified cholesterol at both dose levels at Week 14. Plasma PPCS levels were also reduced. HPβCD was detected at low concentrations in the CSF (maximum, 33 μM) at both dose levels and persisted longer in CSF than in plasma. Total Tau levels in CSF decreased in most subjects. Serum levels of 24(S)-HC, a cholesterol metabolite from the CNS that is exported across the blood-brain barrier and into the circulation, decreased after both the first and seventh doses. Hence, pharmacodynamic assessments in both peripheral and CNS-related tissue show target engagement. While not the aim of the study, subjects reported favorable impacts on their quality of life.
The plasma pharmacokinetics and pharmacodynamics of HPβCD administered at two intravenous dose levels to subjects with NPC1 were comparable to those observed in preclinical models. HPβCD cleared cholesterol from the liver and improved peripheral biomarkers of cholesterol homeostasis. At low CSF concentrations, HPβCD appeared to be pharmacologically active in the CNS based on the increased efflux of 24(S)-HC and reduction in CSF total Tau, a biomarker of CNS neurodegeneration. These data support the initiation of longer-term clinical trials to evaluate the safety and efficacy of intravenous HPβCD in subjects with NPC1. (ClinicalTrials.gov numbers: present trial, NCT02939547; open-label extension of the present trial, NCT 03893071; global pivotal trial, NCT04860960). Niemann-Pick Disease Type C1 (NPC1) is a disorder of intracellular cholesterol and lipid trafficking that leads to the accumulation of cholesterol and lipids in the late endosomal/lysosomal compartment, resulting in systemic manifestations (including hepatosplenomegaly and lung infiltration) and neurodegeneration. Preclinical studies have demonstrated that systemically administered 2-hydroxypropyl-β-cyclodextrin (HPβCD; Trappsol® Cyclo™) restores cholesterol metabolism and homeostasis in peripheral organs and tissues and in the central nervous system (CNS). Here, we assessed the safety, pharmacokinetics, and pharmacodynamics of HPβCD in peripheral tissues and the CNS in adult subjects with NPC1. A Phase 1, randomized, double-blind, parallel group study enrolled 13 subjects with NPC1 who received either 1500 mg/kg or 2500 mg/kg HPβCD intravenously every 2 weeks for a total of 7 doses (14 weeks). Subjects were 18 years or older, with a confirmed diagnosis of NPC1 and evidence of systemic involvement on clinical assessment. Pharmacokinetic evaluations in plasma and cerebrospinal fluid (CSF) were performed at the first and seventh infusions. Pharmacodynamic assessments included biomarkers of systemic cholesterol synthesis (serum lathosterol) and degradation (serum 4β-hydroxycholesterol), secondary sphingomyelin storage (plasma lysosphingomyelin-509, now more accurately referred to as N-palmitoyl-O-phosphocholineserine [PPCS]), and CNS-specific biomarkers of neurodegeneration (CSF total Tau) and cholesterol metabolism (serum 24(S)-hydroxycholesterol [24(S)-HC]). Safety monitoring included assessments of liver and kidney function, infusion related adverse events, and hearing evaluations. Ten subjects completed the study, with 6 at the 1500 mg/kg dose and 4 at the 2500 mg/kg dose. One subject withdrew following the first infusion after experiencing hypersensitivity pneumonitis, and 2 subjects withdrew after meeting a stopping rule related to hearing loss. Overall, HPβCD had an acceptable safety profile. The observed pharmacokinetic profile of HPβCD was similar following the first and seventh infusions, with a plasma half-life of 2 h, a maximum concentration reached at 6 to 8 h, and no evidence of accumulation. Serum biomarkers of cholesterol metabolism showed reduced synthesis and increased degradation. Compared to Baseline, filipin staining of liver tissue showed significant reductions of trapped unesterified cholesterol at both dose levels at Week 14. Plasma PPCS levels were also reduced. HPβCD was detected at low concentrations in the CSF (maximum, 33 μM) at both dose levels and persisted longer in CSF than in plasma. Total Tau levels in CSF decreased in most subjects. Serum levels of 24(S)-HC, a cholesterol metabolite from the CNS that is exported across the blood-brain barrier and into the circulation, decreased after both the first and seventh doses. Hence, pharmacodynamic assessments in both peripheral and CNS-related tissue show target engagement. While not the aim of the study, subjects reported favorable impacts on their quality of life. The plasma pharmacokinetics and pharmacodynamics of HPβCD administered at two intravenous dose levels to subjects with NPC1 were comparable to those observed in preclinical models. HPβCD cleared cholesterol from the liver and improved peripheral biomarkers of cholesterol homeostasis. At low CSF concentrations, HPβCD appeared to be pharmacologically active in the CNS based on the increased efflux of 24(S)-HC and reduction in CSF total Tau, a biomarker of CNS neurodegeneration. These data support the initiation of longer-term clinical trials to evaluate the safety and efficacy of intravenous HPβCD in subjects with NPC1. (ClinicalTrials.gov numbers: present trial, NCT02939547; open-label extension of the present trial, NCT03893071; global pivotal trial, NCT04860960). Niemann-Pick Disease Type C1 (NPC1) is a disorder of intracellular cholesterol and lipid trafficking that leads to the accumulation of cholesterol and lipids in the late endosomal/lysosomal compartment, resulting in systemic manifestations (including hepatosplenomegaly and lung infiltration) and neurodegeneration. Preclinical studies have demonstrated that systemically administered 2-hydroxypropyl-β-cyclodextrin (HPβCD; Trappsol® Cyclo™) restores cholesterol metabolism and homeostasis in peripheral organs and tissues and in the central nervous system (CNS). Here, we assessed the safety, pharmacokinetics, and pharmacodynamics of HPβCD in peripheral tissues and the CNS in adult subjects with NPC1.BACKGROUNDNiemann-Pick Disease Type C1 (NPC1) is a disorder of intracellular cholesterol and lipid trafficking that leads to the accumulation of cholesterol and lipids in the late endosomal/lysosomal compartment, resulting in systemic manifestations (including hepatosplenomegaly and lung infiltration) and neurodegeneration. Preclinical studies have demonstrated that systemically administered 2-hydroxypropyl-β-cyclodextrin (HPβCD; Trappsol® Cyclo™) restores cholesterol metabolism and homeostasis in peripheral organs and tissues and in the central nervous system (CNS). Here, we assessed the safety, pharmacokinetics, and pharmacodynamics of HPβCD in peripheral tissues and the CNS in adult subjects with NPC1.A Phase 1, randomized, double-blind, parallel group study enrolled 13 subjects with NPC1 who received either 1500 mg/kg or 2500 mg/kg HPβCD intravenously every 2 weeks for a total of 7 doses (14 weeks). Subjects were 18 years or older, with a confirmed diagnosis of NPC1 and evidence of systemic involvement on clinical assessment. Pharmacokinetic evaluations in plasma and cerebrospinal fluid (CSF) were performed at the first and seventh infusions. Pharmacodynamic assessments included biomarkers of systemic cholesterol synthesis (serum lathosterol) and degradation (serum 4β-hydroxycholesterol), secondary sphingomyelin storage (plasma lysosphingomyelin-509, now more accurately referred to as N-palmitoyl-O-phosphocholineserine [PPCS]), and CNS-specific biomarkers of neurodegeneration (CSF total Tau) and cholesterol metabolism (serum 24(S)-hydroxycholesterol [24(S)-HC]). Safety monitoring included assessments of liver and kidney function, infusion related adverse events, and hearing evaluations.METHODSA Phase 1, randomized, double-blind, parallel group study enrolled 13 subjects with NPC1 who received either 1500 mg/kg or 2500 mg/kg HPβCD intravenously every 2 weeks for a total of 7 doses (14 weeks). Subjects were 18 years or older, with a confirmed diagnosis of NPC1 and evidence of systemic involvement on clinical assessment. Pharmacokinetic evaluations in plasma and cerebrospinal fluid (CSF) were performed at the first and seventh infusions. Pharmacodynamic assessments included biomarkers of systemic cholesterol synthesis (serum lathosterol) and degradation (serum 4β-hydroxycholesterol), secondary sphingomyelin storage (plasma lysosphingomyelin-509, now more accurately referred to as N-palmitoyl-O-phosphocholineserine [PPCS]), and CNS-specific biomarkers of neurodegeneration (CSF total Tau) and cholesterol metabolism (serum 24(S)-hydroxycholesterol [24(S)-HC]). Safety monitoring included assessments of liver and kidney function, infusion related adverse events, and hearing evaluations.Ten subjects completed the study, with 6 at the 1500 mg/kg dose and 4 at the 2500 mg/kg dose. One subject withdrew following the first infusion after experiencing hypersensitivity pneumonitis, and 2 subjects withdrew after meeting a stopping rule related to hearing loss. Overall, HPβCD had an acceptable safety profile. The observed pharmacokinetic profile of HPβCD was similar following the first and seventh infusions, with a plasma half-life of 2 h, a maximum concentration reached at 6 to 8 h, and no evidence of accumulation. Serum biomarkers of cholesterol metabolism showed reduced synthesis and increased degradation. Compared to Baseline, filipin staining of liver tissue showed significant reductions of trapped unesterified cholesterol at both dose levels at Week 14. Plasma PPCS levels were also reduced. HPβCD was detected at low concentrations in the CSF (maximum, 33 μM) at both dose levels and persisted longer in CSF than in plasma. Total Tau levels in CSF decreased in most subjects. Serum levels of 24(S)-HC, a cholesterol metabolite from the CNS that is exported across the blood-brain barrier and into the circulation, decreased after both the first and seventh doses. Hence, pharmacodynamic assessments in both peripheral and CNS-related tissue show target engagement. While not the aim of the study, subjects reported favorable impacts on their quality of life.RESULTSTen subjects completed the study, with 6 at the 1500 mg/kg dose and 4 at the 2500 mg/kg dose. One subject withdrew following the first infusion after experiencing hypersensitivity pneumonitis, and 2 subjects withdrew after meeting a stopping rule related to hearing loss. Overall, HPβCD had an acceptable safety profile. The observed pharmacokinetic profile of HPβCD was similar following the first and seventh infusions, with a plasma half-life of 2 h, a maximum concentration reached at 6 to 8 h, and no evidence of accumulation. Serum biomarkers of cholesterol metabolism showed reduced synthesis and increased degradation. Compared to Baseline, filipin staining of liver tissue showed significant reductions of trapped unesterified cholesterol at both dose levels at Week 14. Plasma PPCS levels were also reduced. HPβCD was detected at low concentrations in the CSF (maximum, 33 μM) at both dose levels and persisted longer in CSF than in plasma. Total Tau levels in CSF decreased in most subjects. Serum levels of 24(S)-HC, a cholesterol metabolite from the CNS that is exported across the blood-brain barrier and into the circulation, decreased after both the first and seventh doses. Hence, pharmacodynamic assessments in both peripheral and CNS-related tissue show target engagement. While not the aim of the study, subjects reported favorable impacts on their quality of life.The plasma pharmacokinetics and pharmacodynamics of HPβCD administered at two intravenous dose levels to subjects with NPC1 were comparable to those observed in preclinical models. HPβCD cleared cholesterol from the liver and improved peripheral biomarkers of cholesterol homeostasis. At low CSF concentrations, HPβCD appeared to be pharmacologically active in the CNS based on the increased efflux of 24(S)-HC and reduction in CSF total Tau, a biomarker of CNS neurodegeneration. These data support the initiation of longer-term clinical trials to evaluate the safety and efficacy of intravenous HPβCD in subjects with NPC1. (ClinicalTrials.gov numbers: present trial, NCT02939547; open-label extension of the present trial, NCT03893071; global pivotal trial, NCT04860960).CONCLUSIONSThe plasma pharmacokinetics and pharmacodynamics of HPβCD administered at two intravenous dose levels to subjects with NPC1 were comparable to those observed in preclinical models. HPβCD cleared cholesterol from the liver and improved peripheral biomarkers of cholesterol homeostasis. At low CSF concentrations, HPβCD appeared to be pharmacologically active in the CNS based on the increased efflux of 24(S)-HC and reduction in CSF total Tau, a biomarker of CNS neurodegeneration. These data support the initiation of longer-term clinical trials to evaluate the safety and efficacy of intravenous HPβCD in subjects with NPC1. (ClinicalTrials.gov numbers: present trial, NCT02939547; open-label extension of the present trial, NCT03893071; global pivotal trial, NCT04860960). |
| Author | Cox, Gerald F. Hrynkow, Sharon Liu, Benny Hurst, Bryan Hastings, Caroline |
| Author_xml | – sequence: 1 givenname: Caroline surname: Hastings fullname: Hastings, Caroline email: caroline.hastings@ucsf.edu organization: Department of Pediatric Hematology Oncology, UCSF Benioff Children's Hospital Oakland, 747 52nd Street, Oakland, CA 94609-1809, USA – sequence: 2 givenname: Benny surname: Liu fullname: Liu, Benny organization: GI & Liver Clinics, Highland Hospital, Alameda Health System, Highland Hospital, Oakland, CA, USA – sequence: 3 givenname: Bryan surname: Hurst fullname: Hurst, Bryan organization: Boyd Consultants, Electra House, Electra Avenue, Crewe CW1 6GL, UK – sequence: 4 givenname: Gerald F. surname: Cox fullname: Cox, Gerald F. organization: Cyclo Therapeutics, Inc., 6714 NW 16th St., Ste B, Gainesville, FL 32653, USA – sequence: 5 givenname: Sharon surname: Hrynkow fullname: Hrynkow, Sharon organization: Cyclo Therapeutics, Inc., 6714 NW 16th St., Ste B, Gainesville, FL 32653, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36279795$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1186/s13023-019-1207-1 10.1016/j.addr.2007.05.012 10.1016/j.ymgme.2009.06.008 10.1194/jlr.M000257 10.1007/8904_2011_47 10.1371/journal.pone.0006951 10.1002/jimd.12245 10.1186/s12883-015-0511-1 10.1371/journal.pone.0053280 10.1007/s10545-011-9368-7 10.1016/j.ymgme.2021.06.011 10.1074/jbc.M111.326405 10.1186/s13023-018-0785-7 10.1093/hmg/ddab194 10.1002/jps.23077 10.7863/ultra.33.2.197 10.1038/gim.2015.25 10.1016/S0022-2275(20)33390-3 10.1523/JNEUROSCI.1317-11.2011 10.1007/s11033-020-05308-7 10.1517/17425247.2016.1171315 10.2217/clp.12.31 10.1194/jlr.M013789 10.1016/S1474-4422(07)70194-1 10.1177/0883073812464526 10.1074/jbc.R100057200 10.1203/PDR.0b013e3181ee4dd2 10.1016/j.pediatrneurol.2017.12.014 10.1111/jnc.14895 10.1186/1750-1172-5-16 10.1194/jlr.M700525-JLR200 10.1016/j.bbamcr.2008.11.014 10.3390/ijms22126600 10.1007/s00018-020-03706-5 10.1073/pnas.0810895106 10.1212/01.wnl.0000345040.01917.9d 10.1001/jama.2013.281053 10.1212/CPJ.0000000000000399 10.1007/s12640-020-00252-7 10.1016/j.jbior.2018.08.001 10.1126/scitranslmed.3010101 10.1002/ajmg.b.30969 10.1016/S0140-6736(17)31465-4 10.1136/jnnp.2005.086785 10.1194/jlr.D300036-JLR200 10.1007/s10545-012-9583-x 10.1016/S0024-3205(01)01384-4 10.1002/humu.10255 |
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| Keywords | CRP PP UCSF Lysosome Niemann-Pick Disease Type C CK-MB ITT ALT CNS INR URI AEs ABR LC-MS/MS SD t1/2 17D-NPC-CSS CSF Cmax Pharmacodynamics AST HPβCD 24(S)-HC PBMCs GFAP Cyclodextrin NPC1 AUC0- Tmax Vss SAEs Pharmacokinetics IND TEAEs |
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| References | Patterson, Garver, Giugliani, Imrie, Jahnova, Meaney, Nadjar, Vanier, Moneuse, Morand, Rosenberg, Schwierin, Heron (bb0090) 2020; 43 Ramirez, Liu, Aqul, Taylor, Repa, Turley, Dietschy (bb0170) 2011; 52 Karimzadeh, Tonekaboni, Ashrafi, Shafeghati, Rezayi, Salehpour, Ghofrani, Taghdiri, Rahmanifar, Zaman, Aryani, Shoar, Shiva, Tavasoli, Houshmand (bb0100) 2013; 28 Liu, Turley, Burns, Miller, Repa, Dietschy (bb0135) 2009; 106 Belmatoug, Burlina, Giraldo, Hendriksz, Kuter, Mengel, Pastores (bb0095) 2011; 34 Loftsson, Brewster (bb0110) 2012; 101 Berry-Kravis, Chin, Hoffmann, Winston, Stoner, LaGorio, Friedmann, Hernandez, Ory, Porter, O’Keefe (bb0260) 2018; 80 Wassif, Cross, Iben, Sanchez-Pulido, Cougnoux, Platt, Ory, Ponting, Bailey-Wilson, Biesecker, Porter (bb0010) 2016; 18 Liu, Ramirez, Miller, Repa, Turley, Dietschy (bb0165) 2010; 51 Mattsson, Zetterberg, Bianconi, Yanjanin, Fu, Mansson, Porter, Blennow (bb0225) 2012; 3 N.-C.G.W. Group, Wraith, Baumgartner, Bembi, Covanis, Levade, Mengel, Pineda, Sedel, Topcu, Vanier, Widner, Wijburg, Patterson (bb0025) 2009; 98 Hastings, Killilea, Suh, Browne (bb0190) 2011 Ory, Ottinger, Farhat, King, Jiang, Weissfeld, Berry-Kravis, Davidson, Bianconi, Keener, Rao, Soldatos, Sidhu, Walters, Xu, Thurm, Solomon, Pavan, Machielse, Kao, Silber, McKew, Brewer, Vite, Walkley, Austin, Porter (bb0255) 2017; 390 Abel, Walterfang, Fietz, Bowman, Velakoulis (bb0055) 2009; 72 A. World Medical (bb0155) 2013; 310 Cariati, Masuelli, Bei, Tancredi, Frank, D’Arcangelo (bb0060) 2021; 22 Liu (bb0125) 2012; 7 Davidson, Ali, Micsenyi, Stephney, Renault, Dobrenis, Ory, Vanier, Walkley (bb0120) 2009; 4 Lopez de Frutos, Cebolla, Aldamiz-Echevarria, de la Vega, Stanescu, Lahoz, Irun, Giraldo (bb0070) 2020; 47 Reynolds, Linneman, Luna, Warner, Turmelle, Kulkarni, Jiang, Khanna, Shinawi, Porter, Ory, Cole, Dickson (bb0265) 2021; 28 Patterson, Vecchio, Prady, Abel, Wraith (bb0085) 2007; 6 Breilyn, Zhang, Yu, Wasserstein (bb0195) 2021; 28 Hammond, Munkacsi, Sturley (bb0030) 1864; 2019 Pontikis, Davidson, Walkley, Platt, Begley (bb0235) 2013; 36 Yanjanin, Velez, Gropman, King, Bianconi, Conley, Brewer, Solomon, Pavan, Arcos-Burgos, Patterson, Porter (bb0150) 2010; 153B Burkard, Rentsch, von Eckardstein (bb0220) 2004; 45 Brewster, Loftsson (bb0105) 2007; 59 Newton, Milstien, Spiegel (bb0035) 2018; 70 Burton, Ellis, Orr, Chatlani, Yoon, Shoaff, Gallo (bb0075) 2021 Liu, Li, Repa, Turley, Dietschy (bb0130) 2008; 49 Ferraioli, Parekh, Levitov, Filice (bb0160) 2014; 33 Pardridge (bb0240) 2016; 13 Wheeler, Sillence (bb0045) 2020; 153 Imrie, Heptinstall, Knight, Strong (bb0080) 2015; 15 Park, O’Brien, Lundquist, Kraft, Vockley, Karnes, Patterson, Snow (bb0040) 2003; 22 Christian, Byun, Zhong, Wanunu, Marti, Furer, Diederich, Bittman, Rothblat (bb0215) 1999; 40 Rodriguez-Gil, Baxter, Watkins-Chow, Johnson, Davidson, Carlson, Incao, Program, Wallom, Farhat, Platt, Dale, Porter, Pavan (bb0205) 2021; 30 Vite, Bagel, Swain, Prociuk, Sikora, Stein, O’Donnell, Ruane, Ward, Crooks, Li, Mauldin, Stellar, De Meulder, Kao, Ory, Davidson, Vanier, Walkley (bb0200) 2015; 7 Trendelenburg, Vanier, Maza, Millat, Bohner, Munz, Zschenderlein (bb0065) 2006; 77 Walkley, Vanier (bb0050) 2009; 1793 Vanier (bb0020) 2010; 5 Hastings, Vieira, Liu, Bascon, Gao, Wang, Casey, Hrynkow (bb0145) 2019; 14 Raiman, Paucar-Arce, Staretz-Chacham, Spiegel, Boyd, Hastings, Hrynkow (bb0230) 2021 Crumling, Liu, Thomas, Benson, Kanicki, Kabara, Halsey, Dolan, Duncan (bb0245) 2012; 7 Proulx (bb0210) 2021; 78 Patterson, Clayton, Gissen, Anheim, Bauer, Bonnot, Dardis, Dionisi-Vici, Klunemann, Latour, Lourenco, Ory, Parker, Pocovi, Strupp, Vanier, Walterfang, Marquardt (bb0015) 2017; 7 Ramirez, Liu, Taylor, Repa, Burns, Weinberg, Turley, Dietschy (bb0140) 2010; 68 Liu, Ding, Chen, Li, Jiang, Salvi (bb0250) 2020; 38 Aqul, Liu, Ramirez, Pieper, Estill, Burns, Liu, Repa, Turley, Dietschy (bb0175) 2011; 31 Dietschy, Turley (bb0180) 2002; 277 Camargo, Erickson, Garver, Hossain, Carbone, Heidenreich, Blanchard (bb0115) 2001; 70 Geberhiwot, Moro, Dardis, Ramaswami, Sirrs, Marfa, Vanier, Walterfang, Bolton, Dawson, Heron, Stampfer, Imrie, Hendriksz, Gissen, Crushell, Coll, Nadjar, Klunemann, Mengel, Hrebicek, Jones, Ory, Bembi, Patterson, R. International Niemann-Pick Disease (bb0005) 2018; 13 Peake, Vance (bb0185) 2012; 287 Patterson (10.1016/j.ymgme.2022.10.004_bb0015) 2017; 7 Vanier (10.1016/j.ymgme.2022.10.004_bb0020) 2010; 5 Rodriguez-Gil (10.1016/j.ymgme.2022.10.004_bb0205) 2021; 30 Liu (10.1016/j.ymgme.2022.10.004_bb0125) 2012; 7 A. World Medical (10.1016/j.ymgme.2022.10.004_bb0155) 2013; 310 Burkard (10.1016/j.ymgme.2022.10.004_bb0220) 2004; 45 Cariati (10.1016/j.ymgme.2022.10.004_bb0060) 2021; 22 Liu (10.1016/j.ymgme.2022.10.004_bb0165) 2010; 51 Breilyn (10.1016/j.ymgme.2022.10.004_bb0195) 2021; 28 Proulx (10.1016/j.ymgme.2022.10.004_bb0210) 2021; 78 Imrie (10.1016/j.ymgme.2022.10.004_bb0080) 2015; 15 Raiman (10.1016/j.ymgme.2022.10.004_bb0230) 2021 Brewster (10.1016/j.ymgme.2022.10.004_bb0105) 2007; 59 Vite (10.1016/j.ymgme.2022.10.004_bb0200) 2015; 7 Crumling (10.1016/j.ymgme.2022.10.004_bb0245) 2012; 7 Walkley (10.1016/j.ymgme.2022.10.004_bb0050) 2009; 1793 Trendelenburg (10.1016/j.ymgme.2022.10.004_bb0065) 2006; 77 Dietschy (10.1016/j.ymgme.2022.10.004_bb0180) 2002; 277 Camargo (10.1016/j.ymgme.2022.10.004_bb0115) 2001; 70 Patterson (10.1016/j.ymgme.2022.10.004_bb0085) 2007; 6 Liu (10.1016/j.ymgme.2022.10.004_bb0130) 2008; 49 Burton (10.1016/j.ymgme.2022.10.004_bb0075) 2021 N.-C.G.W. Group (10.1016/j.ymgme.2022.10.004_bb0025) 2009; 98 Berry-Kravis (10.1016/j.ymgme.2022.10.004_bb0260) 2018; 80 Liu (10.1016/j.ymgme.2022.10.004_bb0135) 2009; 106 Ferraioli (10.1016/j.ymgme.2022.10.004_bb0160) 2014; 33 Pontikis (10.1016/j.ymgme.2022.10.004_bb0235) 2013; 36 Pardridge (10.1016/j.ymgme.2022.10.004_bb0240) 2016; 13 Patterson (10.1016/j.ymgme.2022.10.004_bb0090) 2020; 43 Park (10.1016/j.ymgme.2022.10.004_bb0040) 2003; 22 Aqul (10.1016/j.ymgme.2022.10.004_bb0175) 2011; 31 Davidson (10.1016/j.ymgme.2022.10.004_bb0120) 2009; 4 Hammond (10.1016/j.ymgme.2022.10.004_bb0030) 1864; 2019 Ramirez (10.1016/j.ymgme.2022.10.004_bb0140) 2010; 68 Newton (10.1016/j.ymgme.2022.10.004_bb0035) 2018; 70 Yanjanin (10.1016/j.ymgme.2022.10.004_bb0150) 2010; 153B Liu (10.1016/j.ymgme.2022.10.004_bb0250) 2020; 38 Mattsson (10.1016/j.ymgme.2022.10.004_bb0225) 2012; 3 Abel (10.1016/j.ymgme.2022.10.004_bb0055) 2009; 72 Loftsson (10.1016/j.ymgme.2022.10.004_bb0110) 2012; 101 Hastings (10.1016/j.ymgme.2022.10.004_bb0190) 2011 Christian (10.1016/j.ymgme.2022.10.004_bb0215) 1999; 40 Wassif (10.1016/j.ymgme.2022.10.004_bb0010) 2016; 18 Peake (10.1016/j.ymgme.2022.10.004_bb0185) 2012; 287 Hastings (10.1016/j.ymgme.2022.10.004_bb0145) 2019; 14 Belmatoug (10.1016/j.ymgme.2022.10.004_bb0095) 2011; 34 Geberhiwot (10.1016/j.ymgme.2022.10.004_bb0005) 2018; 13 Wheeler (10.1016/j.ymgme.2022.10.004_bb0045) 2020; 153 Ramirez (10.1016/j.ymgme.2022.10.004_bb0170) 2011; 52 Lopez de Frutos (10.1016/j.ymgme.2022.10.004_bb0070) 2020; 47 Reynolds (10.1016/j.ymgme.2022.10.004_bb0265) 2021; 28 Ory (10.1016/j.ymgme.2022.10.004_bb0255) 2017; 390 Karimzadeh (10.1016/j.ymgme.2022.10.004_bb0100) 2013; 28 |
| References_xml | – volume: 153 start-page: 674 year: 2020 end-page: 692 ident: bb0045 article-title: Niemann-Pick type C disease: cellular pathology and pharmacotherapy publication-title: J. Neurochem. – volume: 43 start-page: 1060 year: 2020 end-page: 1069 ident: bb0090 article-title: Long-term survival outcomes of patients with Niemann-Pick disease type C receiving miglustat treatment: a large retrospective observational study publication-title: J. Inherit. Metab. Dis. – volume: 15 start-page: 257 year: 2015 ident: bb0080 article-title: Observational cohort study of the natural history of Niemann-Pick disease type C in the UK: a 5-year update from the UK clinical database publication-title: BMC Neurol. – volume: 68 start-page: 309 year: 2010 end-page: 315 ident: bb0140 article-title: Weekly cyclodextrin administration normalizes cholesterol metabolism in nearly every organ of the Niemann-Pick type C1 mouse and markedly prolongs life publication-title: Pediatr. Res. – volume: 33 start-page: 197 year: 2014 end-page: 203 ident: bb0160 article-title: Shear wave elastography for evaluation of liver fibrosis publication-title: J. Ultrasound Med. – year: 2011 ident: bb0190 article-title: Clinical experience and biomarker assessment with intravenous and intrathecal infusions of hydroxypropyl-β-cyclodextrin in identical twin patients with Niemann-Pick Type C disease publication-title: Ara Parseghian Scientific Conference on Niemann-Pick Type C Research – volume: 101 start-page: 3019 year: 2012 end-page: 3032 ident: bb0110 article-title: Cyclodextrins as functional excipients: methods to enhance complexation efficiency publication-title: J. Pharm. Sci. – volume: 22 year: 2021 ident: bb0060 article-title: Neurodegeneration in Niemann-Pick Type C disease: an updated review on pharmacological and non-pharmacological approaches to counteract brain and cognitive impairment publication-title: Int. J. Mol. Sci. – volume: 28 year: 2021 ident: bb0265 article-title: A phase 1/2 open label nonrandomized clinical trial of intravenous 2-hydroxypropyl-beta-cyclodextrin for acute liver disease in infants with Niemann-Pick C1 publication-title: Mol. Genet. Metab. Rep. – volume: 7 start-page: 276ra26 year: 2015 ident: bb0200 article-title: Intracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in feline Niemann-Pick type C1 disease publication-title: Sci. Transl. Med. – volume: 390 start-page: 1758 year: 2017 end-page: 1768 ident: bb0255 article-title: Intrathecal 2-hydroxypropyl-beta-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1-2 trial publication-title: Lancet. – volume: 52 start-page: 688 year: 2011 end-page: 698 ident: bb0170 article-title: Quantitative role of LAL, NPC2, and NPC1 in lysosomal cholesterol processing defined by genetic and pharmacological manipulations publication-title: J. Lipid Res. – volume: 13 start-page: 50 year: 2018 ident: bb0005 article-title: Consensus clinical management guidelines for Niemann-Pick disease type C publication-title: Orphanet J Rare Dis. – volume: 77 start-page: 997 year: 2006 end-page: 998 ident: bb0065 article-title: Niemann-Pick type C disease in a 68-year-old patient publication-title: J. Neurol. Neurosurg. Psychiatry – volume: 310 start-page: 2191 year: 2013 end-page: 2194 ident: bb0155 article-title: World medical association declaration of Helsinki: ethical principles for medical research involving human subjects publication-title: JAMA. – volume: 4 year: 2009 ident: bb0120 article-title: Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression publication-title: PLoS One – volume: 7 start-page: 499 year: 2017 end-page: 511 ident: bb0015 article-title: Recommendations for the detection and diagnosis of Niemann-Pick disease type C: an update publication-title: Neurol. Clin. Pract. – volume: 80 start-page: 24 year: 2018 end-page: 34 ident: bb0260 article-title: Long-term treatment of Niemann-Pick type C1 disease with intrathecal 2-hydroxypropyl-beta-cyclodextrin publication-title: Pediatr. Neurol. – volume: 153B start-page: 132 year: 2010 end-page: 140 ident: bb0150 article-title: Linear clinical progression, independent of age of onset, in Niemann-Pick disease, type C publication-title: Am. J. Med. Genet. B Neuropsychiatr. Genet. – volume: 6 start-page: 765 year: 2007 end-page: 772 ident: bb0085 article-title: Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study publication-title: Lancet Neurol. – volume: 49 start-page: 663 year: 2008 end-page: 669 ident: bb0130 article-title: Genetic variations and treatments that affect the lifespan of the NPC1 mouse publication-title: J. Lipid Res. – volume: 59 start-page: 645 year: 2007 end-page: 666 ident: bb0105 article-title: Cyclodextrins as pharmaceutical solubilizers publication-title: Adv. Drug Deliv. Rev. – volume: 2019 start-page: 1109 year: 1864 end-page: 1123 ident: bb0030 article-title: The complexity of a monogenic neurodegenerative disease: more than two decades of therapeutic driven research into Niemann-Pick type C disease publication-title: Biochim. Biophys. Acta Mol. Cell Biol. Lipids – volume: 45 start-page: 776 year: 2004 end-page: 781 ident: bb0220 article-title: Determination of 24S- and 27-hydroxycholesterol in plasma by high-performance liquid chromatography-mass spectrometry publication-title: J. Lipid Res. – volume: 70 start-page: 82 year: 2018 end-page: 88 ident: bb0035 article-title: Niemann-Pick type C disease: the atypical sphingolipidosis publication-title: Adv. Biol. Regul. – volume: 3 start-page: 45 year: 2012 end-page: 52 ident: bb0225 article-title: Miglustat treatment may reduce cerebrospinal fluid levels of the axonal degeneration marker tau in niemann-pick type C publication-title: JIMD Rep. – volume: 70 start-page: 131 year: 2001 end-page: 142 ident: bb0115 article-title: Cyclodextrins in the treatment of a mouse model of Niemann-Pick C disease publication-title: Life Sci. – volume: 28 year: 2021 ident: bb0195 article-title: Plasma lyso-sphingomyelin levels are positively associated with clinical severity in acid sphingomyelinase deficiency publication-title: Mol. Genet. Metab. Rep. – volume: 30 start-page: 2456 year: 2021 end-page: 2468 ident: bb0205 article-title: Transcriptome of HPbetaCD-treated Niemann-Pick disease type C1 cells highlights GPNMB as a biomarker for therapeutics publication-title: Hum. Mol. Genet. – volume: 28 start-page: 1599 year: 2013 end-page: 1606 ident: bb0100 article-title: Effects of miglustat on stabilization of neurological disorder in niemann-pick disease type C: Iranian pediatric case series publication-title: J. Child Neurol. – volume: 36 start-page: 491 year: 2013 end-page: 498 ident: bb0235 article-title: Cyclodextrin alleviates neuronal storage of cholesterol in Niemann-Pick C disease without evidence of detectable blood-brain barrier permeability publication-title: J. Inherit. Metab. Dis. – volume: 38 start-page: 808 year: 2020 end-page: 823 ident: bb0250 article-title: 2-hydroxypropyl-beta-cyclodextrin ototoxicity in adult rats: rapid onset and massive destruction of both inner and outer hair cells above a critical dose publication-title: Neurotox. Res. – volume: 1793 start-page: 726 year: 2009 end-page: 736 ident: bb0050 article-title: Secondary lipid accumulation in lysosomal disease publication-title: Biochim. Biophys. Acta – volume: 72 start-page: 1083 year: 2009 end-page: 1086 ident: bb0055 article-title: Saccades in adult Niemann-Pick disease type C reflect frontal, brainstem, and biochemical deficits publication-title: Neurology. – volume: 22 start-page: 313 year: 2003 end-page: 325 ident: bb0040 article-title: Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1 publication-title: Hum. Mutat. – volume: 5 start-page: 16 year: 2010 ident: bb0020 article-title: Niemann-Pick disease type C publication-title: Orphanet J Rare Dis. – volume: 277 start-page: 3801 year: 2002 end-page: 3804 ident: bb0180 article-title: Control of cholesterol turnover in the mouse publication-title: J. Biol. Chem. – volume: 31 start-page: 9404 year: 2011 end-page: 9413 ident: bb0175 article-title: Unesterified cholesterol accumulation in late endosomes/lysosomes causes neurodegeneration and is prevented by driving cholesterol export from this compartment publication-title: J. Neurosci. – volume: 78 start-page: 2429 year: 2021 end-page: 2457 ident: bb0210 article-title: Cerebrospinal fluid outflow: a review of the historical and contemporary evidence for arachnoid villi, perineural routes, and dural lymphatics publication-title: Cell. Mol. Life Sci. – volume: 106 start-page: 2377 year: 2009 end-page: 2382 ident: bb0135 article-title: Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1−/− mouse publication-title: Proc. Natl. Acad. Sci. U. S. A. – volume: 13 start-page: 963 year: 2016 end-page: 975 ident: bb0240 article-title: CSF, blood-brain barrier, and brain drug delivery publication-title: Expert Opin. Drug Deliv. – volume: 18 start-page: 41 year: 2016 end-page: 48 ident: bb0010 article-title: High incidence of unrecognized visceral/neurological late-onset Niemann-Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets publication-title: Genet Med. – year: 2021 ident: bb0075 article-title: Estimating the prevalence of Niemann-Pick disease type C (NPC) in the United States publication-title: Mol. Genet. Metab. – volume: 98 start-page: 152 year: 2009 end-page: 165 ident: bb0025 article-title: Recommendations on the diagnosis and management of Niemann-Pick disease type C publication-title: Mol. Genet. Metab. – volume: 47 start-page: 2085 year: 2020 end-page: 2095 ident: bb0070 article-title: New variants in Spanish Niemann-Pick type c disease patients publication-title: Mol. Biol. Rep. – volume: 51 start-page: 933 year: 2010 end-page: 944 ident: bb0165 article-title: Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid publication-title: J. Lipid Res. – volume: 14 start-page: 228 year: 2019 ident: bb0145 article-title: Expanded access with intravenous hydroxypropyl-beta-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis publication-title: Orphanet J Rare Dis. – year: 2021 ident: bb0230 article-title: Update on Safety and Efficacy Results for Phase I/II trial of Trappsol® Cyclo™ Hydroxypropyl Betacyclodextrin Administered Intravenously in Subjects with Niemann-Pick type C1 Disease. Poster #209. in WORLDSymposium – volume: 7 start-page: 289 year: 2012 end-page: 301 ident: bb0125 article-title: Therapeutic potential of cyclodextrins in the treatment of Niemann-Pick type C disease publication-title: Clin. Lipidol. – volume: 40 start-page: 1475 year: 1999 end-page: 1482 ident: bb0215 article-title: Comparison of the capacity of beta-cyclodextrin derivatives and cyclophanes to shuttle cholesterol between cells and serum lipoproteins publication-title: J. Lipid Res. – volume: 7 year: 2012 ident: bb0245 article-title: Hearing loss and hair cell death in mice given the cholesterol-chelating agent hydroxypropyl-beta-cyclodextrin publication-title: PLoS One – volume: 34 start-page: 991 year: 2011 end-page: 1001 ident: bb0095 article-title: Gastrointestinal disturbances and their management in miglustat-treated patients publication-title: J. Inherit. Metab. Dis. – volume: 287 start-page: 9290 year: 2012 end-page: 9298 ident: bb0185 article-title: Normalization of cholesterol homeostasis by 2-hydroxypropyl-beta-cyclodextrin in neurons and glia from Niemann-Pick C1 (NPC1)-deficient mice publication-title: J. Biol. Chem. – volume: 14 start-page: 228 year: 2019 ident: 10.1016/j.ymgme.2022.10.004_bb0145 article-title: Expanded access with intravenous hydroxypropyl-beta-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis publication-title: Orphanet J Rare Dis. doi: 10.1186/s13023-019-1207-1 – volume: 59 start-page: 645 year: 2007 ident: 10.1016/j.ymgme.2022.10.004_bb0105 article-title: Cyclodextrins as pharmaceutical solubilizers publication-title: Adv. Drug Deliv. Rev. doi: 10.1016/j.addr.2007.05.012 – volume: 98 start-page: 152 year: 2009 ident: 10.1016/j.ymgme.2022.10.004_bb0025 article-title: Recommendations on the diagnosis and management of Niemann-Pick disease type C publication-title: Mol. Genet. Metab. doi: 10.1016/j.ymgme.2009.06.008 – volume: 51 start-page: 933 year: 2010 ident: 10.1016/j.ymgme.2022.10.004_bb0165 article-title: Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid publication-title: J. Lipid Res. doi: 10.1194/jlr.M000257 – volume: 3 start-page: 45 year: 2012 ident: 10.1016/j.ymgme.2022.10.004_bb0225 article-title: Miglustat treatment may reduce cerebrospinal fluid levels of the axonal degeneration marker tau in niemann-pick type C publication-title: JIMD Rep. doi: 10.1007/8904_2011_47 – volume: 4 year: 2009 ident: 10.1016/j.ymgme.2022.10.004_bb0120 article-title: Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression publication-title: PLoS One doi: 10.1371/journal.pone.0006951 – volume: 43 start-page: 1060 year: 2020 ident: 10.1016/j.ymgme.2022.10.004_bb0090 article-title: Long-term survival outcomes of patients with Niemann-Pick disease type C receiving miglustat treatment: a large retrospective observational study publication-title: J. Inherit. Metab. Dis. doi: 10.1002/jimd.12245 – volume: 15 start-page: 257 year: 2015 ident: 10.1016/j.ymgme.2022.10.004_bb0080 article-title: Observational cohort study of the natural history of Niemann-Pick disease type C in the UK: a 5-year update from the UK clinical database publication-title: BMC Neurol. doi: 10.1186/s12883-015-0511-1 – volume: 7 year: 2012 ident: 10.1016/j.ymgme.2022.10.004_bb0245 article-title: Hearing loss and hair cell death in mice given the cholesterol-chelating agent hydroxypropyl-beta-cyclodextrin publication-title: PLoS One doi: 10.1371/journal.pone.0053280 – volume: 28 year: 2021 ident: 10.1016/j.ymgme.2022.10.004_bb0265 article-title: A phase 1/2 open label nonrandomized clinical trial of intravenous 2-hydroxypropyl-beta-cyclodextrin for acute liver disease in infants with Niemann-Pick C1 publication-title: Mol. Genet. Metab. Rep. – volume: 34 start-page: 991 year: 2011 ident: 10.1016/j.ymgme.2022.10.004_bb0095 article-title: Gastrointestinal disturbances and their management in miglustat-treated patients publication-title: J. Inherit. Metab. Dis. doi: 10.1007/s10545-011-9368-7 – year: 2021 ident: 10.1016/j.ymgme.2022.10.004_bb0075 article-title: Estimating the prevalence of Niemann-Pick disease type C (NPC) in the United States publication-title: Mol. Genet. Metab. doi: 10.1016/j.ymgme.2021.06.011 – volume: 287 start-page: 9290 year: 2012 ident: 10.1016/j.ymgme.2022.10.004_bb0185 article-title: Normalization of cholesterol homeostasis by 2-hydroxypropyl-beta-cyclodextrin in neurons and glia from Niemann-Pick C1 (NPC1)-deficient mice publication-title: J. Biol. Chem. doi: 10.1074/jbc.M111.326405 – volume: 13 start-page: 50 year: 2018 ident: 10.1016/j.ymgme.2022.10.004_bb0005 article-title: Consensus clinical management guidelines for Niemann-Pick disease type C publication-title: Orphanet J Rare Dis. doi: 10.1186/s13023-018-0785-7 – volume: 30 start-page: 2456 year: 2021 ident: 10.1016/j.ymgme.2022.10.004_bb0205 article-title: Transcriptome of HPbetaCD-treated Niemann-Pick disease type C1 cells highlights GPNMB as a biomarker for therapeutics publication-title: Hum. Mol. Genet. doi: 10.1093/hmg/ddab194 – volume: 101 start-page: 3019 year: 2012 ident: 10.1016/j.ymgme.2022.10.004_bb0110 article-title: Cyclodextrins as functional excipients: methods to enhance complexation efficiency publication-title: J. Pharm. Sci. doi: 10.1002/jps.23077 – volume: 33 start-page: 197 year: 2014 ident: 10.1016/j.ymgme.2022.10.004_bb0160 article-title: Shear wave elastography for evaluation of liver fibrosis publication-title: J. Ultrasound Med. doi: 10.7863/ultra.33.2.197 – volume: 18 start-page: 41 year: 2016 ident: 10.1016/j.ymgme.2022.10.004_bb0010 article-title: High incidence of unrecognized visceral/neurological late-onset Niemann-Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets publication-title: Genet Med. doi: 10.1038/gim.2015.25 – volume: 40 start-page: 1475 year: 1999 ident: 10.1016/j.ymgme.2022.10.004_bb0215 article-title: Comparison of the capacity of beta-cyclodextrin derivatives and cyclophanes to shuttle cholesterol between cells and serum lipoproteins publication-title: J. Lipid Res. doi: 10.1016/S0022-2275(20)33390-3 – volume: 31 start-page: 9404 year: 2011 ident: 10.1016/j.ymgme.2022.10.004_bb0175 article-title: Unesterified cholesterol accumulation in late endosomes/lysosomes causes neurodegeneration and is prevented by driving cholesterol export from this compartment publication-title: J. Neurosci. doi: 10.1523/JNEUROSCI.1317-11.2011 – volume: 47 start-page: 2085 year: 2020 ident: 10.1016/j.ymgme.2022.10.004_bb0070 article-title: New variants in Spanish Niemann-Pick type c disease patients publication-title: Mol. Biol. Rep. doi: 10.1007/s11033-020-05308-7 – volume: 13 start-page: 963 year: 2016 ident: 10.1016/j.ymgme.2022.10.004_bb0240 article-title: CSF, blood-brain barrier, and brain drug delivery publication-title: Expert Opin. Drug Deliv. doi: 10.1517/17425247.2016.1171315 – volume: 7 start-page: 289 year: 2012 ident: 10.1016/j.ymgme.2022.10.004_bb0125 article-title: Therapeutic potential of cyclodextrins in the treatment of Niemann-Pick type C disease publication-title: Clin. Lipidol. doi: 10.2217/clp.12.31 – volume: 52 start-page: 688 year: 2011 ident: 10.1016/j.ymgme.2022.10.004_bb0170 article-title: Quantitative role of LAL, NPC2, and NPC1 in lysosomal cholesterol processing defined by genetic and pharmacological manipulations publication-title: J. Lipid Res. doi: 10.1194/jlr.M013789 – year: 2021 ident: 10.1016/j.ymgme.2022.10.004_bb0230 – volume: 6 start-page: 765 year: 2007 ident: 10.1016/j.ymgme.2022.10.004_bb0085 article-title: Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study publication-title: Lancet Neurol. doi: 10.1016/S1474-4422(07)70194-1 – volume: 28 start-page: 1599 year: 2013 ident: 10.1016/j.ymgme.2022.10.004_bb0100 article-title: Effects of miglustat on stabilization of neurological disorder in niemann-pick disease type C: Iranian pediatric case series publication-title: J. Child Neurol. doi: 10.1177/0883073812464526 – volume: 277 start-page: 3801 year: 2002 ident: 10.1016/j.ymgme.2022.10.004_bb0180 article-title: Control of cholesterol turnover in the mouse publication-title: J. Biol. Chem. doi: 10.1074/jbc.R100057200 – volume: 2019 start-page: 1109 year: 1864 ident: 10.1016/j.ymgme.2022.10.004_bb0030 article-title: The complexity of a monogenic neurodegenerative disease: more than two decades of therapeutic driven research into Niemann-Pick type C disease publication-title: Biochim. Biophys. Acta Mol. Cell Biol. Lipids – volume: 68 start-page: 309 year: 2010 ident: 10.1016/j.ymgme.2022.10.004_bb0140 article-title: Weekly cyclodextrin administration normalizes cholesterol metabolism in nearly every organ of the Niemann-Pick type C1 mouse and markedly prolongs life publication-title: Pediatr. Res. doi: 10.1203/PDR.0b013e3181ee4dd2 – volume: 80 start-page: 24 year: 2018 ident: 10.1016/j.ymgme.2022.10.004_bb0260 article-title: Long-term treatment of Niemann-Pick type C1 disease with intrathecal 2-hydroxypropyl-beta-cyclodextrin publication-title: Pediatr. Neurol. doi: 10.1016/j.pediatrneurol.2017.12.014 – volume: 153 start-page: 674 year: 2020 ident: 10.1016/j.ymgme.2022.10.004_bb0045 article-title: Niemann-Pick type C disease: cellular pathology and pharmacotherapy publication-title: J. Neurochem. doi: 10.1111/jnc.14895 – volume: 5 start-page: 16 year: 2010 ident: 10.1016/j.ymgme.2022.10.004_bb0020 article-title: Niemann-Pick disease type C publication-title: Orphanet J Rare Dis. doi: 10.1186/1750-1172-5-16 – volume: 49 start-page: 663 year: 2008 ident: 10.1016/j.ymgme.2022.10.004_bb0130 article-title: Genetic variations and treatments that affect the lifespan of the NPC1 mouse publication-title: J. Lipid Res. doi: 10.1194/jlr.M700525-JLR200 – volume: 1793 start-page: 726 year: 2009 ident: 10.1016/j.ymgme.2022.10.004_bb0050 article-title: Secondary lipid accumulation in lysosomal disease publication-title: Biochim. Biophys. Acta doi: 10.1016/j.bbamcr.2008.11.014 – volume: 22 year: 2021 ident: 10.1016/j.ymgme.2022.10.004_bb0060 article-title: Neurodegeneration in Niemann-Pick Type C disease: an updated review on pharmacological and non-pharmacological approaches to counteract brain and cognitive impairment publication-title: Int. J. Mol. Sci. doi: 10.3390/ijms22126600 – volume: 78 start-page: 2429 year: 2021 ident: 10.1016/j.ymgme.2022.10.004_bb0210 article-title: Cerebrospinal fluid outflow: a review of the historical and contemporary evidence for arachnoid villi, perineural routes, and dural lymphatics publication-title: Cell. Mol. Life Sci. doi: 10.1007/s00018-020-03706-5 – volume: 106 start-page: 2377 year: 2009 ident: 10.1016/j.ymgme.2022.10.004_bb0135 article-title: Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1−/− mouse publication-title: Proc. Natl. Acad. Sci. U. S. A. doi: 10.1073/pnas.0810895106 – volume: 72 start-page: 1083 year: 2009 ident: 10.1016/j.ymgme.2022.10.004_bb0055 article-title: Saccades in adult Niemann-Pick disease type C reflect frontal, brainstem, and biochemical deficits publication-title: Neurology. doi: 10.1212/01.wnl.0000345040.01917.9d – volume: 310 start-page: 2191 year: 2013 ident: 10.1016/j.ymgme.2022.10.004_bb0155 article-title: World medical association declaration of Helsinki: ethical principles for medical research involving human subjects publication-title: JAMA. doi: 10.1001/jama.2013.281053 – volume: 7 start-page: 499 year: 2017 ident: 10.1016/j.ymgme.2022.10.004_bb0015 article-title: Recommendations for the detection and diagnosis of Niemann-Pick disease type C: an update publication-title: Neurol. Clin. Pract. doi: 10.1212/CPJ.0000000000000399 – volume: 38 start-page: 808 year: 2020 ident: 10.1016/j.ymgme.2022.10.004_bb0250 article-title: 2-hydroxypropyl-beta-cyclodextrin ototoxicity in adult rats: rapid onset and massive destruction of both inner and outer hair cells above a critical dose publication-title: Neurotox. Res. doi: 10.1007/s12640-020-00252-7 – volume: 70 start-page: 82 year: 2018 ident: 10.1016/j.ymgme.2022.10.004_bb0035 article-title: Niemann-Pick type C disease: the atypical sphingolipidosis publication-title: Adv. Biol. Regul. doi: 10.1016/j.jbior.2018.08.001 – volume: 7 start-page: 276ra26 year: 2015 ident: 10.1016/j.ymgme.2022.10.004_bb0200 article-title: Intracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in feline Niemann-Pick type C1 disease publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.3010101 – volume: 153B start-page: 132 year: 2010 ident: 10.1016/j.ymgme.2022.10.004_bb0150 article-title: Linear clinical progression, independent of age of onset, in Niemann-Pick disease, type C publication-title: Am. J. Med. Genet. B Neuropsychiatr. Genet. doi: 10.1002/ajmg.b.30969 – volume: 390 start-page: 1758 year: 2017 ident: 10.1016/j.ymgme.2022.10.004_bb0255 article-title: Intrathecal 2-hydroxypropyl-beta-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1-2 trial publication-title: Lancet. doi: 10.1016/S0140-6736(17)31465-4 – volume: 77 start-page: 997 year: 2006 ident: 10.1016/j.ymgme.2022.10.004_bb0065 article-title: Niemann-Pick type C disease in a 68-year-old patient publication-title: J. Neurol. Neurosurg. Psychiatry doi: 10.1136/jnnp.2005.086785 – volume: 45 start-page: 776 year: 2004 ident: 10.1016/j.ymgme.2022.10.004_bb0220 article-title: Determination of 24S- and 27-hydroxycholesterol in plasma by high-performance liquid chromatography-mass spectrometry publication-title: J. Lipid Res. doi: 10.1194/jlr.D300036-JLR200 – volume: 36 start-page: 491 year: 2013 ident: 10.1016/j.ymgme.2022.10.004_bb0235 article-title: Cyclodextrin alleviates neuronal storage of cholesterol in Niemann-Pick C disease without evidence of detectable blood-brain barrier permeability publication-title: J. Inherit. Metab. Dis. doi: 10.1007/s10545-012-9583-x – year: 2011 ident: 10.1016/j.ymgme.2022.10.004_bb0190 article-title: Clinical experience and biomarker assessment with intravenous and intrathecal infusions of hydroxypropyl-β-cyclodextrin in identical twin patients with Niemann-Pick Type C disease – volume: 28 year: 2021 ident: 10.1016/j.ymgme.2022.10.004_bb0195 article-title: Plasma lyso-sphingomyelin levels are positively associated with clinical severity in acid sphingomyelinase deficiency publication-title: Mol. Genet. Metab. Rep. – volume: 70 start-page: 131 year: 2001 ident: 10.1016/j.ymgme.2022.10.004_bb0115 article-title: Cyclodextrins in the treatment of a mouse model of Niemann-Pick C disease publication-title: Life Sci. doi: 10.1016/S0024-3205(01)01384-4 – volume: 22 start-page: 313 year: 2003 ident: 10.1016/j.ymgme.2022.10.004_bb0040 article-title: Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1 publication-title: Hum. Mutat. doi: 10.1002/humu.10255 |
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| Title | Intravenous 2-hydroxypropyl-β-cyclodextrin (Trappsol® Cyclo™) demonstrates biological activity and impacts cholesterol metabolism in the central nervous system and peripheral tissues in adult subjects with Niemann-Pick Disease Type C1: Results of a phase 1 trial |
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