Top

Orphanet Journal of Rare Diseases

Published in:

Open Access 01-12-2018 | Review

Miglustat in Niemann-Pick disease type C patients: a review

Authors: Mercè Pineda, Mark Walterfang, Marc C. Patterson

Published in: Orphanet Journal of Rare Diseases | Issue 1/2018

Abstract

Objective

Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive, neurodegenerative disease associated with a wide variety of progressive neurological manifestations. Miglustat is indicated for the treatment of progressive neurological manifestations in both adults and children. Since approval in 2009 there has been a vast growth in clinical experience with miglustat. The effectiveness of miglustat has been assessed using a range of measures.

Methods

Comprehensive review of published data from studies of cellular neuropathological markers and structural neurological indices in the brain, clinical impairment/disability, specific clinical neurological manifestations, and patient survival.

Results

Cranial diffusion tensor imaging and magnetic resonance spectroscopy studies have shown reduced levels of choline (a neurodegeneration marker), and choline/N-acetyl aspartate ratio (indicating increased neuronal viability) in the brain during up to 5 years of miglustat therapy, as well as a slowing of reductions in fractional anisotropy (an axonal/myelin integrity marker). A 2-year immunoassay study showed significant reductions in CSF-calbindin during treatment, indicating reduced cerebellar Purkinje cell loss. Magnetic resonance imaging studies have demonstrated a protective effect of miglustat on cerebellar and subcortical structure that correlated with clinical symptom severity. Numerous cohort studies assessing core neurological manifestations (impaired ambulation, manipulation, speech, swallowing, other) using NP-C disability scales indicate neurological stabilization over 2–8 years, with a trend for greater benefits in patients with older (non-infantile) age at neurological onset. A randomized controlled trial and several cohort studies have reported improvements or stabilization of saccadic eye movements during 1–5 years of therapy. Swallowing was also shown to improve/remain stable during the randomized trial (up to 2 years), as well as in long-term observational cohorts (up to 6 years). A meta-analysis of dysphagia – a potent risk factor for aspiration pneumonia and premature death in NP-C – demonstrated a survival benefit with miglustat due to improved/stabilized swallowing function.

Conclusions

The effects of miglustat on neurological NP-C manifestations has been assessed using a range of approaches, with benefits ranging from cellular changes in the brain through to visible clinical improvements and improved survival.

Available only for authorised users

Vanier MT. Niemann-pick disease type C. Orphanet J Rare Dis. 2010;5:16.PubMedPubMedCentralCrossRef

Carstea ED, Morris JA, Coleman KG, Loftus SK, Zhang D, Cummings C, et al. Niemann-pick C1 disease gene: homology to mediators of cholesterol homeostasis. Science. 1997;277:228–31.PubMedCrossRef

Naureckiene S, Sleat DE, Lackland H, Fensom A, Vanier MT, Wattiaux R, et al. Identification of HE1 as the second gene of Niemann-pick C disease. Science. 2000;290:2298–301.PubMedCrossRef

Hendriksz CJ, Anheim M, Bauer P, Bonnot O, Chakrapani A, Corvol JC, et al. The hidden Niemann-pick type C patient: clinical niches for a rare inherited metabolic disease. Curr Med Res Opin. 2017;33:877–90.PubMedCrossRef

Patterson MC, Hendriksz CJ, Walterfang M, Sedel F, Vanier MT, Wijburg F. For the NP-C working group. Recommendations for the diagnosis and management of Niemann-pick disease type C: an update. Mol Genet Metab. 2012;106:330–44.PubMedCrossRef

Wraith JE, Baumgartner MR, Bembi B, Covanis A, Levade T, Mengel E, et al. For the NP-C working group. Recommendations on the diagnosis and management of Niemann-pick disease type C. Mol Genet Metab. 2009;98:152–65.PubMedCrossRef

Wassif CA, Cross JL, Iben J, Sanchez-Pulido L, Cougnoux A, Platt FM, et al. High incidence of unrecognized visceral/neurological late-onset Niemann-pick disease, type C1, predicted by analysis of massively parallel sequencing data sets. Genet Med. 2016;18:41–8.PubMedCrossRef

Bauer P, Balding DJ, Klunemann HH, Linden DE, Ory DS, Pineda M, et al. Genetic screening for Niemann-pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study. Hum Mol Genet. 2013;22:4349–56.PubMedPubMedCentralCrossRef

Schicks J, Muller Vom Hagen J, Bauer P, Beck-Wodl S, Biskup S, Krageloh-Mann I, et al. Niemann-pick type C is frequent in adult ataxia with cognitive decline and vertical gaze palsy. Neurology. 2013;80:1169–70.PubMedCrossRef

10.

Imrie J, Heptinstall L, Knight S, Strong K. 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. BMC Neurol. 2015;15:257.PubMedPubMedCentralCrossRef

11.

Jahnova H, Dvorakova L, Vlaskova H, Hulkova H, Poupetova H, Hrebicek M, Jesina P. Observational, retrospective study of a large cohort of patients with Niemann-pick disease type C in the Czech Republic: a surprisingly stable diagnostic rate spanning almost 40 years. Orphanet J Rare Dis. 2014;9:140.PubMedPubMedCentralCrossRef

12.

Jiang X, Sidhu R, Mydock-McGrane L, Hsu FF, Covey DF, Scherrer DE, et al. Development of a bile acid-based newborn screen for Niemann-pick disease type C. Sci Transl Med. 2016;8:337ra363.CrossRef

13.

Jiang X, Sidhu R, Porter FD, Yanjanin NM, Speak AO, te Vruchte DT, et al. A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann-pick C1 disease from human plasma. J Lipid Res. 2011;52:1435–45.PubMedPubMedCentralCrossRef

14.

Giese AK, Mascher H, Grittner U, Eichler S, Kramp G, Lukas J, et al. A novel, highly sensitive and specific biomarker for Niemann-pick type C1 disease. Orphanet J Rare Dis. 2015;10:78.PubMedPubMedCentralCrossRef

15.

Porter FD, Scherrer DE, Lanier MH, Langmade SJ, Molugu V, Gale SE, et al. Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-pick C1 disease. Sci Transl Med. 2010;2:56ra81.PubMedPubMedCentralCrossRef

16.

Patterson MC, Clayton P, Gissen P, Anheim M, Bauer P, Bonnot O, et al. Recommendations for the detection and diagnosis of Niemann-pick disease type C: an update. Neurol Clin Pract. 2017;7:499–511.PubMedPubMedCentralCrossRef

17.

Vanier MT, Gissen P, Bauer P, Coll MJ, Burlina A, Hendriksz CJ, et al. Diagnostic tests for Niemann-pick disease type C (NP-C): a critical review. Mol Genet Metab. 2016;118:244–54.PubMedCrossRef

18.

Wijburg FA, Sedel F, Pineda M, Hendriksz CJ, Fahey M, Walterfang M, et al. Development of a suspicion index to aid diagnosis of Niemann-pick disease type C. Neurology. 2012;78:1560–7.PubMedCrossRef

19.

Pineda M, Mengel E, Jahnova H, Heron B, Imrie J, Lourenco CM, et al. A suspicion index to aid screening of early-onset Niemann-pick disease type C (NP-C). BMC Pediatr. 2016;16:107.PubMedPubMedCentralCrossRef

20.

Synofzik M, Fleszar Z, Schols L, Just J, Bauer P, Torres Martin JV, Kolb S. Identifying Niemann-pick type C in early-onset ataxia: two quick clinical screening tools. J Neurol. 2016;263:1911–8.PubMedPubMedCentralCrossRef

21.

Wraith JE, Guffon N, Rohrbach M, Hwu WL, Korenke GC, Bembi B, et al. Natural history of Niemann-pick disease type C in a multicentre observational retrospective cohort study. Mol Genet Metab. 2009;98:250–4.PubMedCrossRef

22.

Patterson MC, Mengel E, Wijburg FA, Muller A, Schwierin B, Drevon H, et al. Disease and patient characteristics in NP-C patients: findings from an international disease registry. Orphanet J Rare Dis. 2013;8:12.PubMedPubMedCentralCrossRef

23.

Garver WS, Francis GA, Jelinek D, Shepherd G, Flynn J, Castro G, et al. The national Niemann-pick C1 disease database: report of clinical features and health problems. Am J Med Genet A. 2007;143A:1204–11.PubMedCrossRef

24.

Iturriaga C, Pineda M, Fernandez-Valero EM, Vanier MT, Coll MJ. Niemann-pick C disease in Spain: clinical spectrum and development of a disability scale. J Neurol Sci. 2006;249:1–6.PubMedCrossRef

25.

Bonnot O, Gama CS, Mengel E, Pineda M, Vanier MT, Watson L, et al. Psychiatric and neurological symptoms in patients with Niemann-pick disease type C (NP-C): findings from the international NPC registry. J Inherit Metab Dis. 2016;39:S62–3.

26.

Bonnot O, Klunemann HH, Velten C, Torres Martin JV, Walterfang M. Systematic review of psychiatric signs in Niemann-pick disease type C. World J Biological Psych. 2018:1–13.

27.

Sevin M, Lesca G, Baumann N, Millat G, Lyon-Caen O, Vanier MT, Sedel F. The adult form of Niemann-pick disease type C. Brain. 2007;130:120–33.PubMedCrossRef

28.

Imrie J, Vijayaraghaven S, Whitehouse C, Harris S, Heptinstall L, Church H, et al. Niemann-pick disease type C in adults. J Inherit Metab Dis. 2002;25:491–500.PubMedCrossRef

29.

Crocker AC, Farber S. Niemann-pick disease: a review of eighteen patients. Medicine (Baltimore). 1958;37:1–95.CrossRef

30.

Sylvain M, Arnold DL, Scriver CR, Schreiber R, Shevell MI. Magnetic resonance spectroscopy in Niemann-pick disease type C: correlation with diagnosis and clinical response to cholestyramine and lovastatin. Pediatr Neurol. 1994;10:228–32.PubMedCrossRef

31.

Patterson MC, Di Bisceglie AM, Higgins JJ, Abel RB, Schiffmann R, Parker CC, et al. The effect of cholesterol-lowering agents on hepatic and plasma cholesterol in Niemann-pick disease type C. Neurology. 1993;43:61–4.PubMedCrossRef

32.

Walterfang M, Fahey M, Desmond P, Wood A, Seal ML, Steward C, et al. White and gray matter alterations in adults with Niemann-pick disease type C: a cross-sectional study. Neurology. 2010;75:49–56.PubMedCrossRef

33.

Lloyd-Evans E, Platt FM. Lipids on trial: the search for the offending metabolite in Niemann-pick type C disease. Traffic. 2010;11:419–28.PubMedCrossRef

34.

Vanier MT. Complex lipid trafficking in Niemann-pick disease type C. J Inherit Metab Dis. 2015;38:187–99.PubMedCrossRef

35.

Platt FM, Neises GR, Dwek RA, Butters TD. N-butyldeoxynojirimycin is a novel inhibitor of glycolipid biosynthesis. J Biol Chem. 1994;269:8362–5.PubMed

36.

Miglustat (Zavesca) Summary of Product Characteristics. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2009/11/human_orphan_000562.jsp&mid=WC0b01ac058001d12b&source=homeMedSearch. Accessed 24 May 2018.

37.

Treiber A, Morand O, Clozel M. The pharmacokinetics and tissue distribution of the glucosylceramide synthase inhibitor miglustat in the rat. Xenobiotica. 2007;37:298–314.PubMedCrossRef

38.

Jeyakumar M, Dwek RA, Butters TD, Platt FM. Storage solutions: treating lysosomal disorders of the brain. Nat Rev Neurosci. 2005;6:713–25.PubMed

39.

Zervas M, Somers KL, Thrall MA, Walkley SU. Critical role for glycosphingolipids in Niemann-pick disease type C. Curr Biol. 2001;11:1283–7.PubMedCrossRef

40.

Lachmann RH, te Vruchte D, Lloyd-Evans E, Reinkensmeier G, Sillence DJ, Fernandez-Guillen L, Dwek RA, et al. Treatment with miglustat reverses the lipid-trafficking defect in Niemann-pick disease type C. Neurobiol Dis. 2004;16:654–8.PubMedCrossRef

41.

Patterson MC, Vecchio D, Jacklin E, Abel L, Chadha-Boreham H, Luzy C, et al. Long-term miglustat therapy in children with Niemann-pick disease type C. J Child Neurol. 2010;25:300–5.PubMedCrossRef

42.

Pineda M, Wraith JE, Mengel E, Sedel F, Hwu WL, Rohrbach M, et al. Miglustat in patients with Niemann-pick disease type C (NP-C): a multicenter observational retrospective cohort study. Mol Genet Metab. 2009;98:243–9.PubMedCrossRef

43.

Wraith JE, Vecchio D, Jacklin E, Abel L, Chadha-Boreham H, Luzy C, et al. Miglustat in adult and juvenile patients with Niemann-pick disease type C: long-term data from a clinical trial. Mol Genet Metab. 2010;99:351–7.PubMedCrossRef

44.

Heron B, Valayannopoulos V, Baruteau J, Chabrol B, Ogier H, Latour P, et al. Miglustat therapy in the French cohort of paediatric patients with Niemann-pick disease type C. Orphanet J Rare Dis. 2012;7:36.PubMedPubMedCentralCrossRef

45.

Pineda M, Perez-Poyato MS, O'Callaghan M, Vilaseca MA, Pocovi M, Domingo R, et al. Clinical experience with miglustat therapy in pediatric patients with Niemann-pick disease type C: a case series. Mol Genet Metab. 2010;99:358–66.PubMedCrossRef

46.

Patterson MC, Mengel E, Vanier MT, Schwierin B, Muller A, Cornelisse P, et al. Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-pick disease type C: an observational cohort study. Orphanet J Rare Dis. 2015;10:65.PubMedPubMedCentralCrossRef

47.

Karimzadeh P, Tonekaboni SH, Ashrafi MR, Shafeghati Y, Rezayi A, Salehpour S, et al. Effects of miglustat on stabilization of neurological disorder in niemann-pick disease type C: Iranian pediatric case series. J Child Neurol. 2013;28:1599–606.PubMedCrossRef

48.

Fecarotta S, Romano A, Della Casa R, Del Giudice E, Bruschini D, Mansi G, et al. Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-pick disease type C. Orphanet J Rare Dis. 2015;10:22.PubMedPubMedCentralCrossRef

49.

Frankenburg WK, Dodds JB. The Denver developmental screening test. J Pediatr. 1967;71:181–91.PubMedCrossRef

50.

Bayley N. Bayley scales of infant and toddler development. 3rd ed. PsychCorp: San Antonio; 2006.

51.

Fecarotta S, Amitrano M, Romano A, Della Casa R, Bruschini D, Astarita L, et al. The videofluoroscopic swallowing study shows a sustained improvement of dysphagia in children with Niemann-pick disease type C after therapy with miglustat. Am J Med Genet A. 2011;155A:540–7.PubMedCrossRef

52.

Chien YH, Peng SF, Yang CC, Lee NC, Tsai LK, Huang AC, et al. Long-term efficacy of miglustat in paediatric patients with Niemann-pick disease type C. J Inherit Metab Dis. 2013;36:129–37.PubMedCrossRef

53.

Chien YH, Lee NC, Tsai LK, Huang AC, Peng SF, Chen SJ, Hwu WL. Treatment of Niemann-pick disease type C in two children with miglustat: initial responses and maintenance of effects over 1 year. J Inherit Metab Dis. 2007;30:826.PubMedCrossRef

54.

Abel LA, Walterfang M, Stainer MJ, Bowman EA, Velakoulis D. Longitudinal assessment of reflexive and volitional saccades in Niemann-pick type C disease during treatment with miglustat. Orphanet J Rare Dis. 2015;10:160.PubMedPubMedCentralCrossRef

55.

Abel LA, Bowman EA, Velakoulis D, Fahey MC, Desmond P, Macfarlane MD, et al. Saccadic eye movement characteristics in adult Niemann-pick type C disease: relationships with disease severity and brain structural measures. PLoS One. 2012;7:e50947.PubMedPubMedCentralCrossRef

56.

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.PubMedCrossRef

57.

Bowman EA, Walterfang M, Abel L, Desmond P, Fahey M, Velakoulis D. Longitudinal changes in cerebellar and subcortical volumes in adult-onset Niemann-pick disease type C patients treated with miglustat. J Neurol. 2015;262:2106–14.PubMedCrossRef

58.

Masingue M, Adanyeguh I, Nadjar Y, Sedel F, Galanaud D, Mochel F. Evolution of structural neuroimaging biomarkers in a series of adult patients with Niemann-pick type C under treatment. Orphanet J Rare Dis. 2017;12:22.PubMedPubMedCentralCrossRef

59.

Benussi A, Cotelli MS, Cosseddu M, Bertasi V, Turla M, Salsano E, et al. Preliminary results on long-term potentiation-like cortical plasticity and cholinergic dysfunction after miglustat treatment in Niemann-pick disease type C. JIMD Rep. 2017;36:19–27.PubMedPubMedCentralCrossRef

60.

Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.PubMedCrossRef

61.

Patterson M, Porter F, Vaurio R, Brown T. Longitudinal study of cognition in subjects with Niemann-pick disease type C [abstract 101]. Mol Genet Metab. 2009;96:534.

62.

Zervas M, Dobrenis K, Walkley SU. Neurons in Niemann-pick disease type C accumulate gangliosides as well as unesterified cholesterol and undergo dendritic and axonal alterations. J Neuropathol Exp Neurol. 2001;60:49–64.PubMedCrossRef

63.

Stein VM, Crooks A, Ding W, Prociuk M, O'Donnell P, Bryan C, et al. Miglustat improves purkinje cell survival and alters microglial phenotype in feline Niemann-pick disease type C. J Neuropathol Exp Neurol. 2012;71:434–48.PubMedPubMedCentralCrossRef

64.

Lloyd-Evans E, Pelled D, Riebeling C, Bodennec J, de-Morgan A, Waller H, et al. Glucosylceramide and glucosylsphingosine modulate calcium mobilization from brain microsomes via different mechanisms. J Biol Chem. 2003;278:23594–9.PubMedCrossRef

65.

Lloyd-Evans E, Morgan AJ, He X, Smith DA, Elliot-Smith E, Sillence DJ, et al. Niemann-pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat Med. 2008;14:1247–55.PubMedCrossRef

66.

Lloyd-Evans E, Platt FM. Lysosomal ca(2+) homeostasis: role in pathogenesis of lysosomal storage diseases. Cell Calcium. 2011;50:200–5.PubMedCrossRef

67.

Bradbury A, Bagel J, Sampson M, Farhat N, Ding W, Swain G, et al. Cerebrospinal fluid calbindin d concentration as a biomarker of cerebellar disease progression in Niemann-pick type C1 disease. J Pharmacol Exp Ther. 2016;358:254–61.PubMedPubMedCentralCrossRef

68.

Heitner R, Elstein D, Aerts J, Weely S, Zimran A. Low-dose N-butyldeoxynojirimycin (OGT 918) for type I Gaucher disease. Blood Cells Mol Dis. 2002;28:127–33.PubMedCrossRef

69.

Cox T, Lachmann R, Hollak C, Aerts J, van Weely S, Hrebicek M, et al. Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet. 2000;355:1481–5.PubMedCrossRef

70.

Walkley SU, Suzuki K. Consequences of NPC1 and NPC2 loss of function in mammalian neurons. Biochim Biophys Acta. 2004;1685:48–62.PubMedCrossRef

71.

Suzuki H, Sakiyama T, Harada N, Abe M, Tadokoro M. Pathologic changes of glial cells in murine model of Niemann-pick disease type C: immunohistochemical, lectin-histochemical and ultrastructural observations. Pediatr Int. 2003;45:1–4.PubMedCrossRef

72.

Sarna JR, Larouche M, Marzban H, Sillitoe RV, Rancourt DE, Hawkes R. Patterned Purkinje cell degeneration in mouse models of Niemann-pick type C disease. J Comp Neurol. 2003;456:279–91.PubMedCrossRef

73.

Elleder M, Jirasek A. Neuropathology of various types of Niemann-pick disease. Acta Neuropathol. 1981;7:201–3.CrossRef

74.

German DC, Quintero EM, Liang CL, Ng B, Punia S, Xie C, Dietschy JM. Selective neurodegeneration, without neurofibrillary tangles, in a mouse model of Niemann-pick C disease. J Comp Neurol. 2001;433:415–25.PubMedPubMedCentralCrossRef

75.

Auer I, Schmidt M, Lee V-Y, Curry B, Suzuki K, Shin R-W, et al. Paired helical filament tau (PHFtau) in Niemann-pick type C disease is similar to PHFtau in Alzheimer's disease. Acta Neuropathol. 1995;90:547–51.PubMedCrossRef

76.

Suzuki K, Parker CC, Pentchev PG, Katz D, Ghetti B, D'Agostino AN, Carstea ED. Neurofibrillary tangles in Niemann-pick disease type C. Acta Neuropathol. 1995;89:227–38.PubMedCrossRef

77.

Saito Y, Suzuki K, Nanba E, Yamamoto T, Ohno K, Murayama S. Niemann-pick type C disease: accelerated neurofibrillary tangle formation and amyloid beta deposition associated with apolipoprotein E epsilon 4 homozygosity. Ann Neurol. 2002;52:351–5.PubMedCrossRef

78.

Gropman AL. Expanding the diagnostic and research toolbox for inborn errors of metabolism: the role of magnetic resonance spectroscopy. Mol Genet Metab. 2005;86:2–9.PubMed

79.

Galanaud D, Tourbah A, Lehericy S, Leveque N, Heron B, Billette de Villemeur T, et al. 24 month-treatment with miglustat of three patients with Niemann-pick disease type C: follow up using brain spectroscopy. Mol Genet Metab. 2009;96:55–8.PubMedCrossRef

80.

Sedel F, Chabrol B, Audoin B, Kaphan E, Tranchant C, Burzykowski T, et al. Normalisation of brain spectroscopy findings in Niemann-pick disease type C patients treated with miglustat. J Neurol. 2016;263:927–36.PubMedPubMedCentralCrossRef

81.

Huang JY, Peng SF, Yang CC, Yen KY, Tzen KY, Yen RF. Neuroimaging findings in a brain with Niemann-pick type C disease. J Formos Med Assoc. 2011;110:537–42.PubMedCrossRef

82.

Abel LA, Walterfang M, Fietz M, Bowman EA, Velakoulis D. Saccades in adult Niemann-pick disease type C reflect frontal, brainstem, and biochemical deficits. Neurology. 2009;72:1083–6.PubMedCrossRef

83.

Walterfang M, Macfarlane MD, Looi JC, Abel L, Bowman E, Fahey MC, et al. Pontine-to-midbrain ratio indexes ocular-motor function and illness stage in adult Niemann-pick disease type C. Eur J Neurol. 2012;19:462–7.PubMedCrossRef

84.

Walterfang M, Fahey M, Abel L, Fietz M, Wood A, Bowman E, et al. Size and shape of the corpus callosum in adult Niemann-pick type C reflects state and trait illness variables. AJNR Am J Neuroradiol. 2011;32:1340–6.PubMedCrossRef

85.

Davies-Thompson J, Vavasour I, Scheel M, Rauscher A, Barton JJ. Reduced myelin water in the white matter tracts of patients with Niemann-pick disease type C. AJNR Am J Neuroradiol. 2016;37:1487–9.PubMedCrossRef

86.

Trouard TP, Heidenreich RA, Seeger JF, Erickson RP. Diffusion tensor imaging in Niemann-pick type C disease. Pediatr Neurol. 2005;33:325–30.PubMedCrossRef

87.

Scheel M, Abegg M, Lanyon LJ, Mattman A, Barton JJ. Eye movement and diffusion tensor imaging analysis of treatment effects in a Niemann-pick type C patient. Mol Genet Metab. 2010;99:291–5.PubMedCrossRef

88.

Lau MW, Lee RW, Miyamoto R, Jung ES, Yanjanin Farhat N, Yoshida S, et al. Role of diffusion tensor imaging in prognostication and treatment monitoring in Niemann-pick disease type C1. Diseases. 2016;4:E29.

89.

Bowman EA, Velakoulis D, Desmond P, Walterfang M. Longitudinal changes in white matter fractional anisotropy in adult-onset Niemann-pick disease type C patients treated with miglustat. JIMD Rep. 2017;39:39–43.PubMedPubMedCentralCrossRef

90.

Yanjanin NM, Velez JI, Gropman A, King K, Bianconi SE, Conley SK, et al. Linear clinical progression, independent of age of onset, in Niemann-pick disease, type C. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:132–40.PubMedPubMedCentral

91.

Cologna SM, Jiang XS, Backlund PS, Cluzeau CV, Dail MK, Yanjanin NM, et al. Quantitative proteomic analysis of Niemann-pick disease, type C1 cerebellum identifies protein biomarkers and provides pathological insight. PLoS One. 2012;7:e47845.PubMedPubMedCentralCrossRef

92.

Manganelli F, Dubbioso R, Iodice R, Topa A, Dardis A, Russo CV, et al. Central cholinergic dysfunction in the adult form of Niemann pick disease type C: a further link with Alzheimer's disease? J Neurol. 2014;261:804–8.PubMedCrossRef

93.

Hassan SS, Trenado C, Elben S, Schnitzler A, Groiss SJ. Alteration of cortical excitability and its modulation by Miglustat in Niemann-pick disease type C. J Clin Neurosci. 2018;47:214–7.PubMedCrossRef

94.

Strupp M, Kremmyda O, Adamczyk C, Bottcher N, Muth C, Yip CW, Bremova T. Central ocular motor disorders, including gaze palsy and nystagmus. J Neurol. 2014;261(Suppl 2):S542–58.PubMedCrossRef

95.

Solomon D, Winkelman AC, Zee DS, Gray L, Buttner-Ennever J. Niemann-pick type C disease in two affected sisters: ocular motor recordings and brain-stem neuropathology. Ann N Y Acad Sci. 2005;1039:436–45.PubMedCrossRef

96.

Rottach KG, von Maydell RD, Das VE, Zivotofsky AZ, Discenna AO, Gordon JL, et al. Evidence for independent feedback control of horizontal and vertical saccades from Niemann-pick type C disease. Vision Res. 1997;37:3627–38.PubMedCrossRef

97.

Abe K, Sakai N. Patient with Niemann-pick disease type C: over 20 years' follow-up. BMJ Case Rep. 2017;2017

98.

Hauser SL, Dawson DM, Lehrich JR, Beal MF, Kevy SV, Propper RD, et al. Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH. N Engl J Med. 1983;308:173–80.PubMedCrossRef

99.

Cuisset JM, Sukno S, Trauffler A, Latour P, Dobbelaere D, Michaud L, Vallee L. Impact of miglustat on evolution of atypical presentation of late-infantile-onset Niemann-pick disease type C with early cognitive impairment, behavioral dysfunction, epilepsy, ophthalmoplegia, and cerebellar involvement: a case report. J Med Case Reports. 2016;10:241.CrossRef

100.

Webber D, Klünemann HH. Psychiatric manifestations of Niemann-pick disease. J Inherit Metab Dis. 2011;4:25–31.

101.

Walterfang M, Kornberg A, Adams S, Fietz M, Velakoulis D. Post-ictal psychosis in adolescent Niemann-pick disease type C. J Inherit Metab Dis. 2010;33(Suppl 3):S63–5.PubMedCrossRef

102.

Szakszon K, Szegedi I, Magyar A, Olah E, Andrejkovics M, Balla P, et al. Complete recovery from psychosis upon miglustat treatment in a juvenile Niemann-pick C patient. Eur J Paediatr Neurol. 2014;18:75–8.PubMedCrossRef

103.

104.

Josephs KA, Van Gerpen MW, Van Gerpen JA. Adult onset Niemann-pick disease type C presenting with psychosis. J Neurol Neurosurg Psychiatry. 2003;74:528–9.PubMedPubMedCentralCrossRef

105.

Maubert A, Hanon C, Sedel F. Psychiatric disorders in adult form of Niemann-pick disease type C. L'Encephale. 2016;42:208–13.PubMedCrossRef

106.

Stampfer M, Theiss S, Amraoui Y, Jiang X, Keller S, Ory DS, et al. Niemann-pick disease type C clinical database: cognitive and coordination deficits are early disease indicators. Orphanet J Rare Dis. 2013;8:35.PubMedPubMedCentralCrossRef

107.

Maubert A, Hanon C, Metton JP. Niemann-pick type C disease and psychosis: two siblings. L'Encephale. 2015;41:238–43.PubMedCrossRef

108.

Achenbach TM, Ruffle TM. The child behavior checklist and related forms for assessing behavioral/emotional problems and competencies. Pediatr Rev. 2000;21:265–71.PubMedCrossRef

109.

Santos ML, Raskin S, Telles DS, Lohr A Jr, Liberalesso PB, Vieira SC, Cordeiro ML. Treatment of a child diagnosed with Niemann-pick disease type C with miglustat: a case report in Brazil. J Inherit Metab Dis. 2008;31(Suppl 2):S357–61.PubMedCrossRef

110.

Mattsson N, Mansson JE, Blomqvist M, Campbell E. Niemann-pick type C disease. Rare but possible diagnosis in adult neurology and psychiatry. Lakartidningen. 2013;110:956–7.PubMed

111.

Heitz C, Epelbaum S, Nadjar Y. Cognitive impairment profile in adult patients with Niemann pick type C disease. Orphanet J Rare Dis. 2017;12:166.PubMedPubMedCentralCrossRef

112.

Wechsler D. The Wechsler intelligence scale for children - 4th edition. London: Pearson Assessment; 2004.

113.

Fecarotta S, Astarita L, Bruschini D, Pisani L, Romano A, Del Giudice E, et al. Efficacy of miglustat on the neurological involvement in Italian patients with Niemann-pick disease type C. Mol Genet Metab. 2009;98:70.

114.

Wraith JE, Vecchio D, Jacklin E, Luzy C, Giorgino R, Patterson MC. Disease stability in patients with Niemann-pick disease type C treated with miglustat [abstract 154]. Mol Genet Metab. 2009;96:S46.CrossRef

115.

Reunert J, Fobker M, Kannenberg F, Du Chesne I, Plate M, Wellhausen J, et al. Rapid diagnosis of 83 patients with Niemann pick type C disease and related cholesterol transport disorders by cholestantriol screening. EBioMedicine. 2016;4:170–5.PubMedCrossRef

116.

Welford RW, Garzotti M, Marques Lourenco C, Mengel E, Marquardt T, Reunert J, et al. Plasma lysosphingomyelin demonstrates great potential as a diagnostic biomarker for Niemann-pick disease type C in a retrospective study. PLoS One. 2014;9:e114669.PubMedPubMedCentralCrossRef

117.

Trendelenburg G, Vanier MT, Maza S, Millat G, Bohner G, Munz DL, Zschenderlein R. Niemann-pick type C disease in a 68-year-old patient. J Neurol Neurosurg Psychiatry. 2006;77:997–8.PubMedPubMedCentralCrossRef

118.

Greenberg CR, Barnes JG, Kogan S, Seargeant LE. A rare case of Niemann-pick disease type C without neurological involvement in a 66-year-old patient. Mol Genet Metab Rep. 2015;3:18–20.PubMedPubMedCentralCrossRef

119.

Jan MM, Camfield PR. Nova Scotia Niemann-pick disease (type D): clinical study of 20 cases. J Child Neurol. 1998;13:75–8.PubMedCrossRef

120.

Kelly DA, Portmann B, Mowat AP, Sherlock S, Lake BD. Niemann-pick disease type C: diagnosis and outcome in children, with particular reference to liver disease. J Pediatr. 1993;123:242–7.PubMedCrossRef

121.

Walterfang M, Chien YH, Imrie J, Rushton D, Schubiger D, Patterson MC. Dysphagia as a risk factor for mortality in Niemann-pick disease type C: systematic literature review and evidence from studies with miglustat. Orphanet J Rare Dis. 2012;7:76.PubMedPubMedCentralCrossRef

122.

Temple R. Are surrogate markers adequate to assess cardiovascular disease drugs? JAMA. 1999;282:790–5.PubMedCrossRef

123.

Katz R. Biomarkers and surrogate markers: an FDA perspective. NeuroRx. 2004;1:189–95.PubMedPubMedCentralCrossRef

124.

Di Rocco M, Dardis A, Madeo A, Barone R, Fiumara A. Early miglustat therapy in infantile Niemann-pick disease type C. Pediatr Neurol. 2012;47:40–3.PubMedCrossRef

125.

Brand M, Muller A, Alsop J, van Schaik IN, Bembi B, Hughes D. Results from a 9-year intensive safety surveillance scheme (IS³) in miglustat (Zavesca®)-treated patients. Pharmacoepidemiol Drug Saf. 2015;24:329–33.PubMedCrossRef

126.

Champion H, Ramaswami U, Imrie J, Lachmann RH, Gallagher J, Cox TM, Wraith JE. Dietary modifications in patients receiving miglustat. J Inherit Metab Dis. 2010;33(Suppl 3):S379–83.PubMedCrossRef

127.

Belmatoug N, Burlina A, Giraldo P, Hendriksz CJ, Kuter DJ, Mengel E, Pastores GM. Gastrointestinal disturbances and their management in miglustat-treated patients. J Inherit Metab Dis. 2011;34:991–1001.PubMedCrossRef

128.

Biegstraaten M, Mengel E, Marodi L, Petakov M, Niederau C, Giraldo P, et al. Peripheral neuropathy in adult type 1 Gaucher disease: a 2-year prospective observational study. Brain. 2010;133:2909–19.PubMedCrossRef

129.

Biegstraaten M, van Schaik IN, Aerts JM, Hollak CE. 'Non-neuronopathic' Gaucher disease reconsidered. Prevalence of neurological manifestations in a Dutch cohort of type I Gaucher disease patients and a systematic review of the literature. J Inherit Metab Dis. 2008;31:337–49.PubMedCrossRef

130.

Uc EY, Wenger DA, Jankovic J. Niemann-pick disease type C: two cases and an update. Mov Disord. 2000;15:1199–203.PubMedCrossRef

131.

Alvelius G, Hjalmarson O, Griffiths WJ, Bjorkhem I, Sjovall J. Identification of unusual 7-oxygenated bile acid sulfates in a patient with Niemann-pick disease, type C. J Lipid Res. 2001;42:1571–7.PubMed

132.

Zafeiriou DI, Triantafyllou P, Gombakis NP, Vargiami E, Tsantali C, Michelakaki E. Niemann-pick type C disease associated with peripheral neuropathy. Pediatr Neurol. 2003;29:242–4.PubMedCrossRef

Title: Miglustat in Niemann-Pick disease type C patients: a review
Authors: Mercè Pineda
Mark Walterfang
Marc C. Patterson
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2018
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-018-0844-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Miglustat in Niemann-Pick disease type C patients: a review

Abstract

Objective

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2018

Is sleep apnea underdiagnosed in adult patients with osteogenesis imperfecta? –a single-center cross-sectional study

GAD65 autoantibody characteristics in patients with co-occurring type 1 diabetes and epilepsy may help identify underlying epilepsy etiologies

Key issues in Rett syndrome: emotional, behavioural and autonomic dysregulation (EBAD) - a target for clinical trials

Targeted next-generation sequencing analysis in couples at increased risk for autosomal recessive disorders

From motor performance to participation: a quantitative descriptive study in adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay

What’s new in pontocerebellar hypoplasia? An update on genes and subtypes