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    Polyrotaxane-based systemic delivery of β-cyclodextrins for potentiating therapeutic efficacy in a mouse model of Niemann-Pick type C disease.
    J Control Release 2017 Nov 11. Epub 2017 Nov 11.
    Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan. Electronic address:
    Niemann-Pick type C (NPC) disease is a fatal metabolic disorder characterized by the lysosomal accumulation of cholesterol. Although 2-hydroxypropyl β-cyclodextrin (HP-β-CD) promotes the excretion of cholesterol and prolongs the life span in animal models of NPC disease, it requires extremely high dose. We developed acid-labile β-CD-based polyrotaxanes (PRXs) comprising multiple β-CDs threaded along a polymer chain capped with acid-cleavable stopper molecules for potentiating therapeutic efficacy of β-CD in NPC disease. Read More

    [From the Hallervorden-Spatz eponym to the molecular terminology].
    Orv Hetil 2017 Oct;158(43):1723-1727
    Patológiai Osztály, Markusovszky Egyetemi Oktatókórház Szombathely, Markusovszky u. 5., 9700.
    Introduction And Aim: A combination of Niemann-Pick- and Hallervorden-Spatz diseases led to the death of a 17-year-old boy in 1994. Genetic counseling necessitated further investigations in 2017. Meanwhile, the nomenclature of Hallervorden-Spatz disease has been abandoned. Read More


    Case Report: Ursodeoxycholic acid treatment in Niemann-Pick disease type C; clinical experience in four cases.
    Wellcome Open Res 2017 31;2:75. Epub 2017 Aug 31.
    Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK.
    In this case series, we demonstrate that Ursodeoxycholic acid (UDCA) improves liver dysfunction in Niemann-Pick type C (NPC) and may restore a suppressed cytochrome p450 system. NPC disease is a progressive neurodegenerative lysosomal storage disease caused by mutations in either the NPC1 or NPC2 genes. Liver disease is a common feature presenting either acutely as cholestatic jaundice in the neonatal period, or in later life as elevated liver enzymes indicative of liver dysfunction. Read More

    Hematopoietic stem cell transplantation in Niemann-Pick disease type B monitored by chitotriosidase activity.
    Pediatr Blood Cancer 2017 Nov 1. Epub 2017 Nov 1.
    Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Torino, Italy.
    Here, we report a patient with Niemann-Pick disease type B, with early severe onset of disease and pulmonary involvement, treated with hematopoietic stem cell transplant (HSCT) from a bone marrow matched unrelated donor. We confirm that HSCT is feasible and potentially beneficial for patients with severe phenotype. Noteworthy, we discussed the potential usefulness of the activity of peripheral chitotriosidase for the longitudinal evaluation of HSCT success and effectiveness. Read More

    Corrigendum to "Niemann-Pick Disease Type C Presenting as a Developmental Coordination Disorder with Bullying by Peers in a School-Age Child".
    Case Rep Pediatr 2017 20;2017:4120361. Epub 2017 Sep 20.
    Sanin Rosai Hospital, 1-8-1 Kaike Shinden, Yonago, Tottori 683-8605, Japan.
    [This corrects the article DOI: 10.1155/2015/807591.]. Read More

    The adenosine A2A receptor agonist T1-11 ameliorates neurovisceral symptoms and extends the lifespan of a mouse model of Niemann-Pick type C disease.
    Neurobiol Dis 2017 Oct 25;110:1-11. Epub 2017 Oct 25.
    National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
    Niemann-Pick C is a fatal neurovisceral disorder caused, in 95% of cases, by mutation of NPC1 gene. Therapeutic options are extremely limited and new "druggable" targets are highly warranted. We previously demonstrated that the stimulation of the adenosine A2A receptor (A2AR) normalized the pathological phenotype of cellular models of NPC1. Read More

    Alteration of cortical excitability and its modulation by Miglustat in Niemann-Pick disease type C.
    J Clin Neurosci 2017 Oct 23. Epub 2017 Oct 23.
    Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany; Department of Neurology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany. Electronic address:
    Niemann-Pick type C (NP-C) is a rare, neurodegenerative, lysosomal storage disease. Cortical excitability using different transcranial magnetic stimulation (TMS) protocols together with clinical and neuropsychological testing was longitudinally assessed in a patient with NP-C. Cerebellar inhibition, a measure for the integrity of the cerebello-thalamo-cortical network, was impaired. Read More

    Hydroxypropyl-β-cyclodextrin formulated in nasal chitosan microspheres as candidate therapeutic agent in Alzheimer's disease.
    Curr Drug Deliv 2017 Oct 19. Epub 2017 Oct 19.
    University of Sassari, Department of Chemistry and Pharmacy, via Muroni 23/a, 07100 Sassari. Italy.
    Hydroxypropyl-β-cyclodextrin (HP-CD) is a hydroxyalkyl derivative of native β-cyclodextrin, cyclic oligosaccharide able to form inclusion complexes with many drugs and biomolecules [1]. Cyclodextrins have a possible neuroprotective effect due to their capability to extract and deplete cholesterol from cell membranes [1]. HP-CD is classified as an excipient (cyclodextrins are in fact widely used to improve solubility of poorly water soluble drugs) and it is not been FDA-approved as therapeutic agent. Read More

    2-hydroxypropyl-β-cyclodextrins and the Blood-Brain Barrier: Considerations for Niemann-Pick Disease Type C1.
    Curr Pharm Des 2017 Oct 19. Epub 2017 Oct 19.
    Educational Trainers and Consultants 39 Swains Pond Ave Melrose, MA 02176. United States.
    The rare, chronic, autosomal-recessive lysosomal storage disease Niemann-Pick disease type C1 (NPC1) is characterized by progressively debilitating and ultimately fatal neurological manifestations. There is tremendous need for disease-modifying therapies that address NPC1 neurological pathophysiology, and passage through the blood-brain barrier represents an important consideration for novel NPC1 drugs. Animal investigations of 2-hydroxypropyl--cyclodextrins (HPCD) in NPC1 in mice demonstrated that HPCD does not cross the blood-brain barrier in significant amounts but suggested a potential for these complex oligosaccharides to moderately impact CNS manifestations when administered subcutaneously or intraperitoneally at very high doses; however, safety concerns regarding pulmonary toxicity were raised. Read More

    Differential response of the liver to bile acid treatment in a mouse model of Niemann-Pick disease type C.
    Wellcome Open Res 2017 31;2:76. Epub 2017 Aug 31.
    Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK.
    Niemann-Pick disease type C (NPC) disease is a neurodegenerative lysosomal storage disease caused by mutations in the NPC1 or NPC2 genes. Liver disease is also a common feature of NPC that can present as cholestatic jaundice in the neonatal period. Liver enzymes can remain elevated above the normal range in some patients as they age. Read More

    Aberrant activation of Cdc2/cyclin B1 is involved in initiation of cytoskeletal pathology in murine Niemann-Pick disease type C.
    J Huazhong Univ Sci Technolog Med Sci 2017 Oct 20;37(5):732-739. Epub 2017 Oct 20.
    Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
    Niemann-Pick disease type C (NPC) is a fatal, neurovisceral lipid storage disease, neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons, progressive neuronal loss, neurofibrillary tangles (NFTs) formation, and axonal spheroids (AS). Cytoskeletal pathology including accumulation of hyperphosphorylated cytoskeletal proteins is a neuropathological hallmark of the mouse model of NPC (npc mice). With a goal of elucidating the mechanisms underlying the lesion formation, we investigated the temporal and spatial characteristics of cytoskeletal lesions and the roles of cdc2, cdk4, and cdk5 in lesion formation in young npc mice. Read More

    The Effects of Extracellular Serum Concentration on APP Processing in Npc1-Deficient APP-Overexpressing N2a Cells.
    Mol Neurobiol 2017 Oct 19. Epub 2017 Oct 19.
    Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, T6G 2M8, Canada.
    Amyloid precursor protein (APP) is cleaved by a set of proteases including α-/β-/γ- and recently identified η-secretases, generating C-terminal fragments (CTFs) of varying lengths and amyloid β (Aβ) peptides, which are considered to play a pivotal role in Alzheimer's disease (AD) pathogenesis. Cellular cholesterol content/distribution can regulate the production/clearance of APP metabolites and hence modify AD pathology. To determine the functional relation between endosomal-lysosomal (EL) cholesterol sequestration and APP metabolism, we used our recently developed mouse N2a-ANPC cells that overexpress Swedish mutant human APP in the absence of cholesterol-trafficking Niemann-Pick type C1 (Npc1) protein. Read More

    Cognitive impairment profile in adult patients with Niemann pick type C disease.
    Orphanet J Rare Dis 2017 Oct 18;12(1):166. Epub 2017 Oct 18.
    Neurology Department, Reference Center for Lysosomal Diseases, Hospital of Pitié-Salpêtrière, Paris, France.
    Background: Cognitive impairment is one of the core symptoms of Niemann Pick type C (NPC) disease, but few data concerning the neuropsychological profile of NPC patients are available. The aim of our study was to characterize cognitive impairments in NPC disease and to assess the evolution of these symptoms and the impact of miglustat on cognitive follow-up.

    Methods: We conducted a retrospective study of 21 adult patients diagnosed with NPC disease. Read More

    Hepatitis C virus replication depends on endosomal cholesterol homeostasis.
    J Virol 2017 Oct 18. Epub 2017 Oct 18.
    Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany
    Similar to other positive-strand RNA viruses, hepatitis C virus (HCV) causes massive rearrangements of intracellular membranes, resulting in a membranous web (MW) composed of predominantly double membrane vesicles (DMVs), the presumed sites of RNA replication. DMVs are enriched for cholesterol, but mechanistic details on the source and recruitment of cholesterol to the viral replication organelle are only partially known. Here we focused on selected lipid transfer proteins implicated in direct lipid transfer at various endoplasmic reticulum (ER) - membrane contact sites. Read More

    Microglial involvement in the development of olfactory dysfunction.
    J Vet Sci 2017 Oct 13. Epub 2017 Oct 13.
    Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, South Korea.
    Olfaction is one of the oldest and important senses for life. Olfactory impairment is the most common clinical manifestation among elderly, and its prevalence is sharply increased with aging. Importantly, growing evidence has shown that olfactory dysfunction is the first sign of neurodegeneration, indicating the importance of olfactory assessment as an early diagnostic marker for the detection of neurological disorders. Read More

    Chemosensing of honeybee parasite, Varroa destructor: Transcriptomic analysis.
    Sci Rep 2017 Oct 12;7(1):13091. Epub 2017 Oct 12.
    Institute of Plant Protection, Agricultural Research Organization, The Volcani Center, Rishon LeZion, Israel.
    Chemosensing is a primary sense in nature, however little is known about its mechanism in Chelicerata. As a model organism we used the mite Varroa destructor, a key parasite of honeybees. Here we describe a transcriptomic analysis of two physiological stages for the Varroa foreleg, the site of primary olfactory organ. Read More

    The ceramide activated protein phosphatase Sit4 impairs sphingolipid dynamics, mitochondrial function and lifespan in a yeast model of Niemann-Pick type C1.
    Biochim Biophys Acta 2017 Oct 6;1864(1):79-88. Epub 2017 Oct 6.
    Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal; Departamento de Biologia Molecular, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal. Electronic address:
    The Niemann-Pick type C is a rare neurodegenerative disease that results from loss-of-function point mutations in NPC1 or NPC2, which affect the homeostasis of sphingolipids and sterols in human cells. We have previously shown that yeast lacking Ncr1, the orthologue of human NPC1 protein, display a premature ageing phenotype and higher sensitivity to oxidative stress associated with mitochondrial dysfunctions and accumulation of long chain bases. In this study, a lipidomic analysis revealed specific changes in the levels of ceramide species in ncr1Δ cells, including decreases in dihydroceramides and increases in phytoceramides. Read More

    Niemann-Pick disease type C in the newborn period: a single-center experience.
    Eur J Pediatr 2017 Dec 27;176(12):1669-1676. Epub 2017 Sep 27.
    Department of Pediatric Gastroenterology, Hacettepe University Children's Hospital, Sihhiye, 06100, Ankara, Turkey.
    Niemann-Pick disease type C (NPC) is a neurovisceral lysosomal storage disorder with a great variation in clinical spectrum and age at presentation. Clinical features of 10 NPC patients who presented in the newborn period between 1993 and 2015 at our center were retrospectively analyzed. Males and females were equally distributed; there was a history of parental consanguinity (n = 8) and first-degree relative with NPC (n = 3). Read More

    Role of Diffusion Tensor Imaging in Prognostication and Treatment Monitoring in Niemann-Pick Disease Type C1.
    Diseases 2016 Sep 8;4(3). Epub 2016 Sep 8.
    National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
    Niemann-Pick Disease, type C1 (NPC1) is a rapidly progressive neurodegenerative disorder characterized by cholesterol sequestration within late endosomes and lysosomes, for which no reliable imaging marker exists for prognostication and management. Cerebellar volume deficits are found to correlate with disease severity and diffusion tensor imaging (DTI) of the corpus callosum and brainstem, which has shown that microstructural disorganization is associated with NPC1 severity. This study investigates the utility of cerebellar DTI in clinical severity assessment. Read More

    Pharmacological blockade of cholesterol trafficking by cepharanthine in endothelial cells suppresses angiogenesis and tumor growth.
    Cancer Lett 2017 Nov 18;409:91-103. Epub 2017 Sep 18.
    Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China; Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; The SJ Yan and HJ Mao Laboratory of Chemical Biology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. Electronic address:
    Cholesterol is an important modulator of membrane protein function and signaling in endothelial cells, thus making it an emerging target for anti-angiogenic agents. In this study, we employed a phenotypic screen that detects intracellular cholesterol distribution in endothelial cells (HUVEC) and identified 13 existing drugs as cholesterol trafficking inhibitors. Cepharanthine, an approved drug for anti-inflammatory and cancer management use, was amongst the candidates, which was selected for in-depth mechanistic studies to link cholesterol trafficking and angiogenesis. Read More

    The role of epigenetics in lysosomal storage disorders: Uncharted territory.
    Mol Genet Metab 2017 Aug 1. Epub 2017 Aug 1.
    Medical Genetics Branch, NHGRI, NIH, Bethesda, MD, United States.
    The study of the contribution of epigenetic mechanisms, including DNA methylation, histone modifications, and microRNAs, to human disease has enhanced our understanding of different cellular processes and diseased states, as well as the effect of environmental factors on phenotypic outcomes. Epigenetic studies may be particularly relevant in evaluating the clinical heterogeneity observed in monogenic disorders. The lysosomal storage disorders are Mendelian disorders characterized by a wide spectrum of associated phenotypes, ranging from neonatal presentations to symptoms that develop in late adulthood. Read More

    Psychiatric and neurological symptoms in patients with Niemann-Pick disease type C (NP-C): Findings from the International NPC Registry.
    World J Biol Psychiatry 2017 Oct 9:1-10. Epub 2017 Oct 9.
    h Pediatric and Adolescent Medicine , Mayo Clinic , Rochester , MN , USA.
    Objectives: Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease that should be recognised by psychiatrists as a possible underlying cause of psychiatric abnormalities. This study describes NP-C patients who had psychiatric manifestations at enrolment in the international NPC Registry, a unique multicentre, prospective, observational disease registry.

    Methods: Treating physicians' data entries describing psychiatric manifestations in NPC patients were coded and grouped by expert psychiatrists. Read More

    Exacerbating and reversing lysosomal storage diseases: from yeast to humans.
    Microb Cell 2017 Aug 25;4(9):278-293. Epub 2017 Aug 25.
    Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032.
    Lysosomal storage diseases (LSDs) arise from monogenic deficiencies in lysosomal proteins and pathways and are characterized by a tissue-wide accumulation of a vast variety of macromolecules, normally specific to each genetic lesion. Strategies for treatment of LSDs commonly depend on reduction of the offending metabolite(s) by substrate depletion or enzyme replacement. However, at least 44 of the ~50 LSDs are currently recalcitrant to intervention. Read More

    Lipidomic and Transcriptomic Basis of Lysosomal Dysfunction in Progranulin Deficiency.
    Cell Rep 2017 Sep;20(11):2565-2574
    Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:
    Defective lysosomal function defines many neurodegenerative diseases, such as neuronal ceroid lipofuscinoses (NCL) and Niemann-Pick type C (NPC), and is implicated in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD-TDP) with progranulin (PGRN) deficiency. Here, we show that PGRN is involved in lysosomal homeostasis and lipid metabolism. PGRN deficiency alters lysosome abundance and morphology in mouse neurons. Read More

    A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Flux.
    ACS Nano 2017 Sep 12. Epub 2017 Sep 12.
    Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.
    Lipid accumulation within the lumen of endolysosomal vesicles is observed in various pathologies including atherosclerosis, liver disease, neurological disorders, lysosomal storage disorders, and cancer. Current methods cannot measure lipid flux specifically within the lysosomal lumen of live cells. We developed an optical reporter, composed of a photoluminescent carbon nanotube of a single chirality, that responds to lipid accumulation via modulation of the nanotube's optical band gap. Read More

    Steryl ester synthesis, storage and hydrolysis: A contribution to sterol homeostasis.
    Biochim Biophys Acta 2017 Dec 6;1862(12):1534-1545. Epub 2017 Sep 6.
    Institute of Biochemistry, Graz University of Technology, NaWi Graz, Austria. Electronic address:
    Sterols are essential lipids of all eukaryotic cells, appearing either as free sterols or steryl esters. Besides other regulatory mechanisms, esterification of sterols and hydrolysis of steryl esters serve to buffer both an excess and a lack of free sterols. In this review, the esterification process, the storage of steryl esters and their mobilization will be described. Read More

    The Report of Three Rare Cases of the Niemann-pick Disease in Birjand, South Khorasan, Eastern Iran.
    Iran J Child Neurol 2017 ;11(3):53-56
    Pediatrics Endocrinology Department, Mashhad University of Medical Sciences, Mashhad, Iran.
    Niemann-Pick disease type C (NP-C) is a rare neurovisceral and irreversible disease leading to premature death and disabling neurological signs. This autosomal recessive disease with incidence rate of 1:120000 is caused by mutations in either the NPC1 or the NPC2 gene, which leads to accumulation of cholesterol in body tissues especially brain and progressive neurological symptoms. NP-C is characterized by nonspecific visceral, neurological and psychiatric manifestations in infants. Read More

    Quantitative Analysis of the Proteome Response to the Histone Deacetylase Inhibitor (HDACi) Vorinostat in Niemann-Pick Type C1 disease.
    Mol Cell Proteomics 2017 Nov 31;16(11):1938-1957. Epub 2017 Aug 31.
    From the ‡Department of Chemical Physiology and Cell and Molecular Biology, The Scripps Research Institute, 10550, North Torrey Pines Road, La Jolla, California 92037;
    Niemann-Pick type C (NPC) disease is an inherited, progressive neurodegenerative disorder principally caused by mutations in the NPC1 gene. NPC disease is characterized by the accumulation of unesterified cholesterol in the late endosomes (LE) and lysosomes (Ly) (LE/Ly). Vorinostat, a histone deacetylase inhibitor (HDACi), restores cholesterol homeostasis in fibroblasts derived from NPC patients; however, the exact mechanism by which Vorinostat restores cholesterol level is not known yet. Read More

    Activation of PKC triggers rescue of NPC1 patient specific iPSC derived glial cells from gliosis.
    Orphanet J Rare Dis 2017 Aug 25;12(1):145. Epub 2017 Aug 25.
    Albrecht-Kossel-Institute for Neuroregeneration (AKos), University Medicine Rostock, Gehlsheimer Straße 20, 18147, Rostock, Germany.
    Background: Niemann-Pick disease Type C1 (NPC1) is a rare progressive neurodegenerative disorder caused by mutations in the NPC1 gene. The pathological mechanisms, underlying NPC1 are not yet completely understood. Especially the contribution of glial cells and gliosis to the progression of NPC1, are controversially discussed. Read More

    Patient with Niemann-Pick disease type C: over 20 years' follow-up.
    BMJ Case Rep 2017 Aug 22;2017. Epub 2017 Aug 22.
    Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan.
    We report a 37-year-old woman with Niemann-Pick disease type C (NPC) 1. At the age of 8 years, she presented slow running followed by both fingers dystonia at the age of 10 years. At the age of 16 years, she developed declined scholastic achievement. Read More

    FORWARD: A Registry and Longitudinal Clinical Database to Study Fragile X Syndrome.
    Pediatrics 2017 Jun;139(Suppl 3):S183-S193
    Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York.
    Background And Objective: Advances in the care of patients with fragile X syndrome (FXS) have been hampered by lack of data. This deficiency has produced fragmentary knowledge regarding the natural history of this condition, healthcare needs, and the effects of the disease on caregivers. To remedy this deficiency, the Fragile X Clinic and Research Consortium was established to facilitate research. Read More

    Prospective Turkish Cohort Study to Investigate the Frequency of Niemann-Pick Disease Type C Mutations in Consanguineous Families with at Least One Homozygous Family Member.
    Mol Diagn Ther 2017 Aug 14. Epub 2017 Aug 14.
    Department of Medical Genetics, Hacettepe University Faculty of Medicine, Ankara, Turkey.
    Background: Niemann-Pick disease Type C (NP-C) is a rare, autosomal recessive lysosomal storage disorder caused by mutations in NPC1 or NPC2 genes. Diagnosis of NP-C can be challenging and is frequently delayed. Identifying mutations in individuals with NP-C and their relatives enables genetic counseling and prenatal diagnosis and may support earlier diagnosis. Read More

    Intrathecal 2-hydroxypropyl-β-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1-2 trial.
    Lancet 2017 Oct 10;390(10104):1758-1768. Epub 2017 Aug 10.
    Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD USA. Electronic address:
    Background: Niemann-Pick disease, type C1 (NPC1) is a lysosomal storage disorder characterised by progressive neurodegeneration. In preclinical testing, 2-hydroxypropyl-β-cyclodextrins (HPβCD) significantly delayed cerebellar Purkinje cell loss, slowed progression of neurological manifestations, and increased lifespan in mouse and cat models of NPC1. The aim of this study was to assess the safety and efficacy of lumbar intrathecal HPβCD. Read More

    Utility of rapid whole exome sequencing in the diagnosis of neonatal Niemann Pick disease type C presenting with fetal hydrops and liver failure.
    Cold Spring Harb Mol Case Stud 2017 Aug 11. Epub 2017 Aug 11.
    Boston Children's Hospital;
    Rapid whole exome sequencing (rWES) is increasingly used in critically ill newborn infants to inform about diagnosis, clinical management and prognosis. Here we report a male newborn infant with hydrops, pancytopenia and acute liver failure who was listed for liver transplantation. Given the acuity of the presentation, the procedure related morbidity and mortality and lack of diagnosis we employed rWES in the proband and both parents with a turn-around time of 10 business days. Read More

    Limited benefits of presymptomatic cord blood transplantation in neurovisceral acid sphingomyelinase deficiency (ASMD) intermediate type.
    Eur J Paediatr Neurol 2017 Nov 29;21(6):907-911. Epub 2017 Jul 29.
    Reference Centre for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, Paris, France; UMR1141, PROTECT, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. Electronic address:
    Acid sphingomyelinase (ASM) deficient Niemann-Pick disease is a lysosomal storage disorder resulting from mutations in the SMPD1 gene. The clinical spectrum distinguishes a severe infantile neurological form (type A), a non-neurological visceral form (type B) and a rare intermediate neurovisceral form. We report the first case of presymptomatic cord blood transplantation in a child with the intermediate type of ASM deficiency due to a homozygous Tyr369Cys mutation, whose affected elder brother had developed neurodevelopmental delay from 19 months of age, and had died from severe visceral complications at the age of 3. Read More

    3.3 Å structure of Niemann-Pick C1 protein reveals insights into the function of the C-terminal luminal domain in cholesterol transport.
    Proc Natl Acad Sci U S A 2017 Aug 7;114(34):9116-9121. Epub 2017 Aug 7.
    Laboratory of Cell Biology, The Rockefeller University, New York, NY 10065;
    Niemann-Pick C1 (NPC1) and NPC2 proteins are indispensable for the export of LDL-derived cholesterol from late endosomes. Mutations in these proteins result in Niemann-Pick type C disease, a lysosomal storage disease. Despite recent reports of the NPC1 structure depicting its overall architecture, the function of its C-terminal luminal domain (CTD) remains poorly understood even though 45% of NPC disease-causing mutations are in this domain. Read More

    The cholesterol transport inhibitor U18666A inhibits type I feline coronavirus infection.
    Antiviral Res 2017 Sep 3;145:96-102. Epub 2017 Aug 3.
    Laboratory of Veterinary Infectious Disease, School of Veterinary Medicine, Kitasato University, Towada, Japan. Electronic address:
    Feline infectious peritonitis (FIP) is a feline coronavirus (FCoV)-induced fatal disease in wild and domestic cats. FCoV exists in two serotypes. Type I FCoV is the dominant serotype worldwide. Read More

    LC-MS/MS multiplex analysis of lysosphingolipids in plasma and amniotic fluid: A novel tool for the screening of sphingolipidoses and Niemann-Pick type C disease.
    PLoS One 2017 27;12(7):e0181700. Epub 2017 Jul 27.
    Service de Biochimie et Biologie Moléculaire Grand Est, Unité Médicale Pathologies Métaboliques, Erythrocytaires et Dépistage Périnatal, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Bron, France.
    Background: The biological diagnosis of sphingolipidoses currently relies on the measurement of specific enzymatic activities and/or genetic studies. Lysosphingolipids have recently emerged as potential biomarkers of sphingolipidoses and Niemann-Pick type C in plasma.

    Methodology: We developed a sensitive and specific method enabling the simultaneous quantification of lysosphingolipids by LC-MS/MS: lysoglobotriaosylceramide for Fabry disease, lysohexosylceramide (i. Read More

    NMR analysis reveals significant differences in the plasma metabolic profiles of Niemann Pick C1 patients, heterozygous carriers, and healthy controls.
    Sci Rep 2017 Jul 24;7(1):6320. Epub 2017 Jul 24.
    Department of Pharmacology, De Montfort University, Leicester, UK.
    Niemann-Pick type C1 (NPC1) disease is a rare autosomal recessive, neurodegenerative lysosomal storage disorder, which presents with a range of clinical phenotypes and hence diagnosis remains a challenge. In view of these difficulties, the search for a novel, NPC1-specific biomarker (or set of biomarkers) is a topic of much interest. Here we employed high-resolution (1)H nuclear magnetic resonance spectroscopy coupled with advanced multivariate analysis techniques in order to explore and seek differences between blood plasma samples acquired from NPC1 (untreated and miglustat treated), heterozygote, and healthy control subjects. Read More

    Newborn Screening for Lysosomal Storage Disorders in Illinois: The Initial 15-Month Experience.
    J Pediatr 2017 Nov 17;190:130-135. Epub 2017 Jul 17.
    Newborn Screening Laboratory, Illinois Department of Public Health, Chicago, IL; Division of Laboratory Services, Tennessee Department of Health, Nashville, TN.
    Objectives: To assess the outcomes of newborn screening for 5 lysosomal storage disorders (LSDs) in the first cohort of infants tested in the state of Illinois.

    Study Design: Tandem mass spectrometry was used to assay for the 5 LSD-associated enzymes in dried blood spot specimens obtained from 219 973 newborn samples sent to the Newborn Screening Laboratory of the Illinois Department of Public Health in Chicago.

    Results: The total number of cases with a positive diagnosis and the incidence for each disorder were as follows: Fabry disease, n = 26 (1 in 8454, including the p. Read More

    The role of macrophages in interstitial lung diseases: Number 3 in the Series "Pathology for the clinician" Edited by Peter Dorfmüller and Alberto Cavazza.
    Eur Respir Rev 2017 Sep 19;26(145). Epub 2017 Jul 19.
    Unit of Pathologic Anatomy, Azienda ULSS 13, Hospital of Dolo, Dolo, Italy.
    The finding of collections of macrophages/histiocytes in lung biopsy and bronchoalveolar lavage is relatively common in routine practice. This morphological feature in itself is pathological, but the exact clinical significance and underlying disease should be evaluated together with clinical data, functional respiratory and laboratory tests and imaging studies.Morphological characteristics of macrophages and their distribution along the different pulmonary structures should be examined carefully by pathologists. Read More

    Longitudinal Changes in White Matter Fractional Anisotropy in Adult-Onset Niemann-Pick Disease Type C Patients Treated with Miglustat.
    JIMD Rep 2017 Jul 15. Epub 2017 Jul 15.
    Neuropsychiatry Unit, Royal Melbourne Hospital, Melbourne, VIC, Australia.
    Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment currently available is miglustat, an iminosugar that inhibits the accumulation of lipid metabolites in neurons and other cells. This longitudinal diffusion tensor imaging (DTI) study examined how the rate of white matter change differed between treated and non-treated adult-onset NPC patient groups. Read More

    Modulating cancer cell survival by targeting intracellular cholesterol transport.
    Br J Cancer 2017 Aug 11;117(4):513-524. Epub 2017 Jul 11.
    Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
    Background: Demand for cholesterol is high in certain cancers making them potentially sensitive to therapeutic strategies targeting cellular cholesterol homoeostasis. A potential approach involves disruption of intracellular cholesterol transport, which occurs in Niemann-Pick disease as a result of acid sphingomyelinase (ASM) deficiency. Hence, a class of lysosomotropic compounds that were identified as functional ASM inhibitors (FIASMAs) might exhibit chemotherapeutic activity by disrupting cancer cell cholesterol homoeostasis. Read More

    Patient With Niemann-Pick Type C Presenting With a Jaw Mass Characterized With Lymph Node Involvement by Niemann-Pick Cells.
    J Pediatr Hematol Oncol 2017 Jul 7. Epub 2017 Jul 7.
    *Division of Pediatric Metabolism and Nutrition †Department of Pathology ‡Division of Pediatric Haematology and Oncology, Gazi University Hospital, Ankara, Turkey.
    Niemann-Pick type C disease (NPC) is an autosomal recessive disorder resulting in accumulation of unesterified lysosomal cholesterol. An 8-year-old girl with NPC disease had a painless, rigid, and fixed mass measuring 3 cm in diameter located on the left angular region of mandibula. The mass biopsy showed lipid-laden phagocytic cells infiltrating the lymph node consistent with Niemann-Pick cells. Read More

    Overview of immune abnormalities in lysosomal storage disorders.
    Immunol Lett 2017 Aug 4;188:79-85. Epub 2017 Jul 4.
    Centro Italiano Macula, Rome, Italy.
    The critical relevance of the lysosomal compartment for normal cellular function can be proved by numbering the clinical phenotypes that arise in lysosomal storage disorders (LSDs), a group of around 70 different monogenic autosomal or X-linked syndromes, caused by specific lysosomal enzyme deficiencies: all LSDs are characterized by progressive accumulation of heterogeneous biologic materials in the lysosomes of various parts of the body such as viscera, skeleton, skin, heart, and central nervous system. At least a fraction of LSDs has been associated with mixed abnormalities involving the immune system, while some patients with LSDs may result more prone to autoimmune phenomena. A large production of proinflammatory cytokines has been observed in Gaucher and Fabry diseases, and wide different autoantibody production has been also reported in both. Read More

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