Systemic administration of 2-hydroxypropyl-β-cyclodextrin to symptomatic Npc1-deficient mice slows cholesterol sequestration in the major organs and improves liver function

Clinical and Experimental Pharmacology and Physiology

Volumn 41, Issue 10, 2014, Pages 780-787

  Lopez, Adam M ^a   Terpack, Sandi J ^a   Posey, Kenneth S ^a   Liu, Benny ^a   Ramirez, Charina M ^a   Turley, Stephen D ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Biliary cholesterol; Brain; Hepatosplenomegaly; Lifespan; Lung; Lysosomal storage disease; Relative organ weight

Indexed keywords

2 HYDROXYPROPYL BETA CYCLODEXTRIN; ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; CHOLESTEROL; SODIUM CHLORIDE; 2-HYDROXYPROPYL-BETA-CYCLODEXTRIN; BETA CYCLODEXTRIN DERIVATIVE; NPC1 PROTEIN, MOUSE; PROTEIN;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CHOLESTEROL LIVER LEVEL; CHOLESTEROL METABOLISM; CONTROLLED STUDY; DISEASE COURSE; FEMALE; LIFESPAN; LIVER FAILURE; LIVER FUNCTION; LIVER FUNCTION TEST; MALE; MOUSE; NIEMANN PICK DISEASE; NONHUMAN; ORGAN WEIGHT; SPLEEN; TREATMENT DURATION; TREATMENT RESPONSE; ANIMAL; BAGG ALBINO MOUSE; DISEASE MODEL; DRUG EFFECTS; LIVER; METABOLISM; NIEMANN-PICK DISEASE, TYPE C; ORGAN SIZE; PROCEDURES;

ANIMALS; BETA-CYCLODEXTRINS; CHOLESTEROL; DISEASE MODELS, ANIMAL; LIVER; LIVER FUNCTION TESTS; MICE; MICE, INBRED BALB C; NIEMANN-PICK DISEASE, TYPE C; ORGAN SIZE; PROTEINS;

EID: 84911033540     PISSN: 03051870     EISSN: 14401681     Source Type: Journal    
DOI: 10.1111/1440-1681.12285     Document Type: Article

References (34)

1. Vanier MT. Niemann-Pick disease type C. Orphanet J. Rare Dis. 2010; 5: 16.
2. Xie X, Brown MS, Shelton JM, Richardson JA, Goldstein JL, Liang G. Amino acid substitution in NPC1 that abolishes cholesterol binding reproduces phenotype of complete NPC1 deficiency in mice. Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 330-5.
3. Erickson RP. Current controversies in Niemann-Pick C1 disease: Steroids or gangliosides; neurons or neurons and glia. J. Appl. Genet. 2013; 54: 215-24.
4. Helquist P, Wiest O. Current status of drug therapy development for Niemann-Pick type C disease. Drugs Fut. 2009; 34: 315-31.
5. Liu B. Therapeutic potential of cyclodextrins in the treatment of Niemann-Pick type C disease. Clin. Lipidol. 2012; 7: 289-301.
6. Vance JE, Karten B. Niemann-Pick C disease and mobilization of lysosomal cholesterol by cyclodextrin. J. Lipid Res. 2014; 55: 1609-21.
7. Patterson MC, Vecchio D, Prady H, Abel L, Wraith JE. Miglustat for treatment of Niemann-Pick C disease: A randomised controlled study. Lancet Neurol. 2007; 6: 765-72.
8. Liu B, Turley SD, Burns DK, Miller AM, Repa JJ, Dietschy JM. Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-/- mouse. Proc. Natl. Acad. Sci. U.S.A. 2009; 106: 2377-82.
9. Liu B, Ramirez CM, Miller AM, Repa JJ, Turley SD, Dietschy JM. Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid. J. Lipid Res. 2010; 51: 933-44.
10. Ramirez CM, Liu B, Taylor AM et al. Weekly cyclodextrin administration normalizes cholesterol metabolism in nearly every organ of the Niemann-Pick type C1 mouse and markedly prolongs life. Pediatr. Res. 2010; 68: 309-15.
11. Aqul A, Liu B, Ramirez CM et al. Unesterified cholesterol accumulation in late endosomes/lysosomes causes neurodegeneration and is prevented by driving cholesterol export from this compartment. J. Neurosci. 2011; 31: 9404-13.
12. Ramirez CM, Liu B, Aqul A et al. Quantitative role of LAL, NPC2, and NPC1 in lysosomal cholesterol processing defined by genetic and pharmacological manipulations. J. Lipid Res. 2011; 52: 688-98.
13. Beltroy EP, Liu B, Dietschy JM, Turley SD. Lysosomal unesterified cholesterol content correlates with liver cell death in murine Niemann-Pick type C disease. J. Lipid Res. 2007; 48: 869-81.
14. Kuriyama M, Yoshida H, Suzuki M, Fujiyama J, Igata A. Lysosomal acid lipase deficiency in rats. Lipid analyses and lipase activities in liver and spleen. J. Lipid Res. 1990; 31: 1605-12.
15. Du H, Heur M, Duanmu M et al. Lysosomal acid lipase-deficient mice: Depletion of white and brown fat, severe hepatosplenomegaly, and shortened life span. J. Lipid Res. 2001; 42: 489-500.
16. Balwani M, Breen C, Enns GM et al. Clinical effect and safety profile of recombinant human lysosomal acid lipase in patients with cholesteryl ester storage disease. Hepatology 2013; 58: 950-7.
17. Sun Y, Xu YH, Du H et al. Reversal of advanced disease in lysosomal acid lipase deficient mice: A model for lysosomal acid lipase deficiency disease. Mol. Genet. Metab. 2014; 112: 229-41.
18. Ward S, O'Donnell P, Fernandez S, Vite CH. 2-Hydroxypropyl-beta-cyclodextrin raises hearing threshold in normal cats and in cats with Niemann-Pick type C disease. Pediatr. Res. 2010; 68: 52-6.
19. Crumling MA, Liu L, Thomas PV et al. Hearing loss and hair cell death in mice given the cholesterol-chelating agent hydroxypropyl-beta-cyclodextrin. PLoS ONE 2012; 7: e53280.
20. Matsuo M, Togawa M, Hirabaru K et al. Effects of cyclodextrin in two patients with Niemann-Pick Type C disease. Mol. Genet. Metab. 2013; 108: 76-81.
21. Chien YH, Shieh YD, Yang CY, Lee NC, Hwu WL. Lung toxicity of hydroxypropyl-β-cyclodextrin infusion. Mol. Genet. Metab. 2013; 109: 231-2.
22. Gould S, Scott RC. 2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CD): A toxicology review. Food Chem. Toxicol. 2005; 43: 1451-9.
23. Irie T, Uekama K. Pharmaceutical applications of cyclodextrins. III. Toxicological issues and safety evaluation. J. Pharm. Sci. 1997; 86: 147-62.
24. Muralidhar A, Borbon IA, Esharif DM et al. Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1-/- mice. Mol. Genet. Metab. 2011; 103: 142-7.
25. Rosenbaum AI, Zhang G, Warren JD, Maxfield FR. Endocytosis of beta-cyclodextrins is responsible for cholesterol reduction in Niemann-Pick type C mutant cells. Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 5477-82.
26. Plazzo AP, Hofer CT, Jicsinszky L et al. Uptake of a fluorescent methyl-beta-cyclodextrin via clathrin-dependent endocytosis. Chem. Phys. Lipids 2012; 165: 505-11.
27. Taylor AM, Liu B, Mari Y, Liu B, Repa JJ. Cyclodextrin mediates rapid changes in lipid balance in Npc1-/- mice without carrying cholesterol through the bloodstream. J. Lipid Res. 2012; 53: 2331-42.
28. Roszell BR, Tao JQ, Yu KJ et al. Pulmonary abnormalities in animal models due to Niemann-Pick type C1 (NPC1) or C2 (NPC2) disease. PLoS ONE 2013; 8: e67084.
29. Ramirez CM, Lopez AM, Le LQ, Posey KS, Weinberg AG, Turley SD. Ontogenic changes in lung cholesterol metabolism, lipid content, and histology in mice with Niemann-Pick type C disease. Biochim. Biophys. Acta 2014; 1841: 54-61.
30. Nielsen GK, Dagnaes-Hansen F, Holm IE et al. Protein replacement therapy partially corrects the cholesterol-storage phenotype in a mouse model of Niemann-Pick type C2 disease. PLoS ONE 2011; 6: e27287.
31. Collins CJ, McCauliff LA, Hyun SH et al. Synthesis, characterization, and evaluation of pluronic-based beta-cyclodextrin polyrotaxanes for mobilization of accumulated cholesterol from Niemann-Pick type C fibroblasts. Biochemistry 2013; 52: 3242-53.
32. Tamura A, Yui N. Lysosomal-specific cholesterol reduction by biocleavable polyrotaxanes for ameliorating Niemann-Pick type C disease. Sci. Rep. 2014; 4: 4356.
33. Schwarz M, Russell DW, Dietschy JM, Turley SD. Marked reduction in bile acid synthesis in cholesterol 7α-hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia. J. Lipid Res. 1998; 39: 1833-43.
34. Tesla R, Wolf HP, Xu P et al. Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. U.S.A. 2012; 109: 17016-21.