3,680 results match your criteria Niemann-Pick Disease
Biomed Rep 2018 Dec 3;9(6):545. Epub 2018 Oct 3.
[This corrects the article DOI: 10.3892/br.2018. Read More
EMBO J 2018 Dec 7. Epub 2018 Dec 7.
Department of Molecular Neuropathology, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Madrid, Spain
Neuropathic lysosomal storage disorders (LSDs) present with activated pro-inflammatory microglia. However, anti-inflammatory treatment failed to improve disease pathology. We characterise the mechanisms underlying microglia activation in Niemann-Pick disease type A (NPA). Read More
Eur J Pharm Sci 2018 Dec 3. Epub 2018 Dec 3.
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary. Electronic address:
A new renaissance started in the research and application of cyclodextrins a few years ago. 2-Hydroxypropyl-beta-cyclodextrin (HPBCD) is used in the formulation of drugs and recently orphan designation was granted for the treatment of Niemann-Pick disease, type C. HPBCD is considered to be safe, but the exact mechanism of action and side effects are not completely explained. Read More
Nat Nanotechnol 2018 Dec 3. Epub 2018 Dec 3.
Department of Chemistry, The University of Chicago, Chicago, IL, USA.
Lysosomes are multifunctional, subcellular organelles with roles in plasma membrane repair, autophagy, pathogen degradation and nutrient sensing. Dysfunctional lysosomes underlie Alzheimer's disease, Parkinson's disease and rare lysosomal storage diseases, but their contributions to these pathophysiologies are unclear. Live imaging has revealed lysosome subpopulations with different physical characteristics including dynamics, morphology or cellular localization. Read More
Handb Exp Pharmacol 2018 Nov 27. Epub 2018 Nov 27.
Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA.
Sphingosine, ceramide, sphingosine-1-phosphate, and other related sphingolipids have emerged as important bioactive molecules involved in a variety of key cellular processes such as cell growth, differentiation, apoptosis, exosome release, and inter- and intracellular cell communication, making the pathways of sphingolipid metabolism a key domain in maintaining cell homeostasis (Hannun and Obeid, Trends Biochem Sci 20:73-77, 1995; Hannun and Obeid, Nat Rev Mol Cell Biol 9:139-150, 2008; Kosaka et al., J Biol Chem 288:10849-10859, 2013). Various studies have determined that these pathways play a central role in regulating intracellular production of ceramide and the other bioactive sphingolipids and hence are an important component of signaling in various diseases such as cancer, diabetes, and neurodegenerative and cardiovascular diseases (Chaube et al. Read More
BMC Med Genet 2018 Nov 20;19(1):203. Epub 2018 Nov 20.
Department of Biochemistry, Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia.
Background: Obesity is one of the main causes of morbidity and mortality worldwide. More than 120 genes have been shown to be associated with obesity related phenotypes. The aim of this study was to determine the effect of selected genetic polymorphisms in Uncoupling protein 1 (UCP1) and Niemann-Pick C1 (NPC1) genes in an obese population in Saudi Arabia. Read More
Int J Mol Sci 2018 Nov 14;19(11). Epub 2018 Nov 14.
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.
Niemann⁻Pick type C (NPC) disease is a rare neurovisceral cholesterol storage disorder that arises from loss of function mutations in the or genes. Soon after birth, some patients present with an aggressive hepatosplenomegaly and cholestatic signs. Histopathologically, the liver presents with large numbers of foam cells; however, their role in disease pathogenesis has not been explored in depth. Read More
Exp Mol Med 2018 Nov 14;50(11):149. Epub 2018 Nov 14.
Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, 08826, South Korea.
We previously demonstrated that the direct transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the dentate gyrus ameliorated the neurological symptoms of Niemann-Pick type C1 (NPC1)-mutant mice. However, the clinical presentation of NPC1-mutant mice was not fully understood with a molecular mechanism. Here, we found 14,15-epoxyeicosatrienoic acid (14,15-EET), a cytochrome P450 (CYP) metabolite, from hUCB-MSCs and the cerebella of NPC1-mutant mice and investigated the functional consequence of this metabolite. Read More
Int J Mol Sci 2018 Nov 12;19(11). Epub 2018 Nov 12.
Department of Anatomy, University of Rostock, 18057 Rostock, Germany.
Introduction: Olfactory impairment is one of the earliest symptoms in neurodegenerative disorders that has also been documented in Niemann-Pick disease type C1 (NPC1). NPC1 is a very rare, neurovisceral lipid storage disorder, characterized by a deficiency of gene function that leads to progressive neurodegeneration. Here, we compared the pathologic effect of defective gene on the vomeronasal neuroepithelium (VNE) with that of the olfactory epithelium (OE) in an NPC1 mouse model. Read More
J Heart Lung Transplant 2018 Oct 16. Epub 2018 Oct 16.
Division of Pulmonary and Critical Care Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Mol Genet Metab 2018 Dec 30;125(4):345-350. Epub 2018 Oct 30.
Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, DHHS, Bethesda, MD 20892, USA. Electronic address:
Niemann-Pick disease, type C1 (NPC1) is an inborn error of metabolism that results in endolysosomal accumulation of unesterified cholesterol. Clinically, NPC1 manifests as cholestatic liver disease in the newborn or as a progressive neurogenerative condition characterized by cerebellar ataxia and cognitive decline. Currently there are no FDA approved therapies for NPC1. Read More
Antiviral Res 2018 Dec 1;160:151-164. Epub 2018 Nov 1.
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City, Mexico. Electronic address:
Despite the importance of Dengue virus (DENV) infection in human health, there is not a fully effective vaccine or antiviral treatment against the infection. Since lipids such as cholesterol are required during DENV infection, its uptake and synthesis are increased in infected cells. Ezetimibe is an FDA-approved drug that reduces cholesterol uptake by inhibiting the endocytosis through Niemman-Pick C1-Like 1 (NPC1L1) receptor, expressed on the membrane of enterocytes and hepatocytes. Read More
J Cell Biochem 2018 Nov 2. Epub 2018 Nov 2.
Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.
Background: Niemann Pick type C (NPC) lysosomal disorder is linked to the disruption of cholesterol transport. Recent data suggest that the molecular background of this disease is more complex. It was found that accumulation of cholesterol and glycolipids in the late endosomal/lysosomal compartment of NPC1 cells may affect mitochondrial functions. Read More
Parkinsonism Relat Disord 2018 Oct 26. Epub 2018 Oct 26.
Division of Neurology, Department of Clinical Medicine, Universidade Federal do Ceará, Brazil; Neurology Service, Hospital Geral de Fortaleza, Fortaleza, Ceará, Brazil; Center of Health Sciences, Universidade Estadual do Ceará, Brazil. Electronic address:
Background: There are few studies reporting characteristics of patients with cerebellar ataxias in the Brazilian population. The aim of this study was to provide a detailed neurological description of patients with hereditary ataxia followed by a neurology outpatient service in Brazil.
Methods: Neurological and clinical evaluation of patients with hereditary ataxia was performed at a neurology service outpatient clinic of a hospital in Northeast Brazil between October 2013 and January 2015. Read More
Int J Mol Sci 2018 Nov 1;19(11). Epub 2018 Nov 1.
Departamento de Bioquímica, Instituto Biofisika (UPV/EHU, CSIC), Universidad del País Vasco, Apdo.644, 48080 Bilbao, Spain.
Cholesterol is an essential component of cell barrier formation and signaling transduction involved in many essential physiologic processes. For this reason, cholesterol metabolism must be tightly controlled. Cell cholesterol is mainly acquired from two sources: Dietary cholesterol, which is absorbed in the intestine and, intracellularly synthesized cholesterol that is mainly synthesized in the liver. Read More
Am J Physiol Lung Cell Mol Physiol 2018 Oct 25. Epub 2018 Oct 25.
Microbiology and Immunology, Geisel School of Medicine at Dartmouth, United States.
Pseudomonas aeruginosa secretes outer membrane vesicles (OMVs) that fuse with cholesterol-rich lipid rafts in the apical membrane of airway epithelial cells and decrease wt-CFTR Cl secretion. Herein, we tested the hypothesis that a reduction of the cholesterol content of CF human airway epithelial cells by cyclodextrins reduces the inhibitory effect of OMVs on VX-809-stimulated Phe508del CFTR Cl secretion. Primary CF bronchial epithelial cells, and CFBE cells were treated with vehicle, hydroxypropyl-beta-cyclodextrin (HPbCD) or methyl-beta-cyclodextrin (MbCD) and the effects of OMVs secreted by Pseudomonas aeruginosa on VX-809 stimulated Phe508del CFTR Cl secretion were measured in Ussing chambers. Read More
Rev Colomb Psiquiatr 2018 Oct - Dec;47(4):244-251. Epub 2017 Jun 17.
Service Universitaire de Psychiatrie de l'Enfant et de l'Adolescent, Université de Nantes, Nantes, Francia.
Some diseases secondary to inborn errors of metabolism are associated with psychiatric disorders or minor neurological symptoms. The existence of some cases with exclusively psychiatric symptoms represents a diagnostic and therapeutic challenge. The aim of this article is to describe seven treatable neurometabolic disorders that should be taken into account in the psychiatric consultation as they manifest with psychiatric symptoms that mask the organic origin of the disorder. Read More
Orphanet J Rare Dis 2018 Oct 1;13(1):175. Epub 2018 Oct 1.
Reference Centre for Lysosomal Diseases (CRML), Department of Pediatric Neurology, and Sorbonne Université, GRC n°19, Pathologies Congénitales du Cervelet-LeucoDystrophies, AP-HP, Hôpital Armand Trousseau, F-75012, Paris, France.
Background: Niemann-Pick disease type C (NP-C) is a neurodegenerative lysosomal lipid storage disease caused by autosomal recessive mutations in the NPC1 or NPC2 genes. The clinical presentation and evolution of NP-C and the effect of miglustat treatment are described in the largest cohort of patients with adolescent/adult-onset NP-C studied to date.
Methods: Observational study based on clinical chart data from adult patients with NP-C (> 18 year old) diagnosed in France between 1990 and 2015. Read More
Cell Death Dis 2018 Oct 3;9(10):1019. Epub 2018 Oct 3.
Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, 37208, USA.
Niemann-Pick type C (NPC) disease is a fatal hereditary neurodegenerative disorder characterized by a massive accumulation of cholesterol in lysosomes and late endosomes due to a defect in intracellular cholesterol trafficking. Dysfunction in intracellular cholesterol trafficking is responsible for about 50 rare inherited lysosomal storage disorders including NPC. The lysosomal proteins NPC1 and NPC2 play a crucial role in trafficking of cholesterol from late endosomes and lysosomes to other cellular compartments. Read More
Sci Transl Med 2018 Oct;10(461)
Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
The abnormal accumulation of lipids within the endolysosomal lumen occurs in many conditions, including lysosomal storage disorders, atherosclerosis, nonalcoholic fatty liver disease (NAFLD), and drug-induced phospholipidosis. Current methods cannot monitor endolysosomal lipid content in vivo, hindering preclinical drug development and research into the mechanisms linking endolysosomal lipid accumulation to disease progression. We developed a single-walled carbon nanotube-based optical reporter that noninvasively measures endolysosomal lipid accumulation via bandgap modulation of its intrinsic near-infrared emission. Read More
J Lipid Res 2018 Dec 28;59(12):2446-2455. Epub 2018 Sep 28.
Department of Chemistry University of Illinois at Chicago, Chicago, IL 60607
Mass spectrometry imaging (MSI) is a tool to rapidly map the spatial location of analytes without the need for tagging or a reporter system. Niemann-Pick disease type C1 (NPC1) is a neurodegenerative, lysosomal storage disorder characterized by accumulation of unesterified cholesterol and sphingolipids in the endo-lysosomal system. Here, we use MSI to visualize lipids including cholesterol in cerebellar brain tissue from the NPC1 symptomatic mouse model and unaffected controls. Read More
Sensors (Basel) 2018 Sep 27;18(10). Epub 2018 Sep 27.
Austrian Institute of Technology GmbH, Biosensor Technologies, Konrad-Lorenzstraße, 24, 3430 Tulln, Austria.
Odour perception has been the object of fast growing research interest in the last three decades. Parallel to the study of the corresponding biological systems, attempts are being made to model the olfactory system with electronic devices. Such projects range from the fabrication of individual sensors, tuned to specific chemicals of interest, to the design of multipurpose smell detectors using arrays of sensors assembled in a sort of artificial nose. Read More
J Child Neurol 2018 Dec 28;33(14):882-887. Epub 2018 Sep 28.
2 Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
Inherited leukodystrophies are a group of diseases affecting central nervous system myelin that lead to death or significant health problems. Although for most leukodystrophies there are no curative treatments, for a handful of diseases hematopoietic stem cell transplantation (HSCT; bone marrow transplant) can stop disease progression, and if initiated in a timely fashion, prevent many or all neurologic and other systems involvement. However, HSCT is a complex procedure with significant morbidity and mortality risks. Read More
Liver Int 2018 Sep 27. Epub 2018 Sep 27.
Department of Medical Microbiology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Background & Aims: Despite high-risk behaviour, 10%-20% of HCV multiple exposed individuals remain uninfected (MEU), whilst the remainder become infected (MEI). We hypothesize that host factors play a role in HCV susceptibility. We aimed to identify polymorphisms in host genes that encode for proteins involved in viral entry: CD81, Scavenger receptor 1 (SR-1), Low-density lipoprotein receptor (LDL-R), Claudin-1 (CLDN1), Occludin (OCLN) and Niemann-Pick C1-like 1 (NPC1L1). Read More
Acta Neuropathol Commun 2018 Sep 24;6(1):98. Epub 2018 Sep 24.
Department of Communication Sciences and Disorders, Northwestern University, Evanston, IL, 60208, USA.
Niemann-Pick Type C1 (NPC1) disease is a fatal neurovisceral disorder caused by dysfunction of NPC1 protein, which plays a role in intracellular cholesterol trafficking. The cholesterol-chelating agent, 2-hydroxypropyl-β-cyclodextrin (HPβCD), is currently undergoing clinical trials for treatment of this disease. Though promising in alleviating neurological symptoms, HPβCD causes irreversible hearing loss in NPC1 patients and outer hair cell (OHC) death in animal models. Read More
J Lipid Res 2018 Nov 21;59(11):2181-2187. Epub 2018 Sep 21.
Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan
Intestinal cholesterol absorption is a key regulator of systemic cholesterol homeostasis. Excessive dietary cholesterol and its intestinal uptake lead to hypercholesterolemia, a major risk factor for cardiovascular disease. Intestinal cholesterol uptake is mediated by Niemann-Pick C1-like 1 (NPC1L1), a transmembrane protein localized in membrane microdomains (lipid rafts) enriched in gangliosides and cholesterol. Read More
J Med Case Rep 2018 Sep 18;12(1):272. Epub 2018 Sep 18.
Biochemistry and Molecular Biology Department, Faculty of Medicine-Al-Quds University, Abu Dis-East Jerusalem, Palestine.
Background: Niemann-Pick disease is caused by reduced level of the lysosomal enzyme acid sphingomyelinase. Children can survive between 2 and 12 years based on the disease type. Two main types are well known: type A and B. Read More
Macromol Rapid Commun 2018 Sep 14:e1800557. Epub 2018 Sep 14.
Department of Chemistry, Istanbul Technical University, Maslak, Istanbul, 34469, Turkey.
Over the last decade, cyclodextrins (CDs) have gained considerable attention as a potential therapeutic intervention in the treatment of the rare genetic condition Niemann-Pick type C disease (NPC). However, the oligosaccharide in its monomeric form suffers from serious side effects, especially from a pharmacokinetic and biodistribution standpoint. CD-based macromolecular systems hold great promise to overcome such limitations and might provide an improved therapeutic approach in reducing cholesterol accumulation in NPC. Read More
J Appl Genet 2018 Sep 13. Epub 2018 Sep 13.
Department of Pediatrics, University of Arizona, Tucson, AZ, 85724-5073, USA.
Early onset Niemann-Pick C diseases are extremely rare, especially Niemann-Pick C2. Perhaps unusually for autosomal recessive diseases, heterozygotes for mutations in NPC1 manifest many biological variations. NPC2 deficiency has large effects on fertility. Read More
Adv Biol Regul 2018 Dec 28;70:82-88. Epub 2018 Aug 28.
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA. Electronic address:
Niemann-Pick type C (NPC) disease is a lysosomal storage disorder resulting from mutations in either the NPC1 (95%) or NPC2 (5%) genes. NPC typically presents in childhood with visceral lipid accumulation and complex progressive neurodegeneration characterized by cerebellar ataxia, dysphagia, and dementia, resulting in a shortened lifespan. While cholesterol is widely acknowledged as the principal storage lipid in NPC, multiple species of sphingolipids accumulate as well. Read More
Clin Biochem 2018 Nov 8;61:40-44. Epub 2018 Sep 8.
Sandor Lifesciences Pvt. Ltd, Hyderabad, India. Electronic address:
Objective: Plasma chitotriosidase is a documented biomarker for certain lysosomal storage disorders. However, its clinical utility for prenatal samples is not elucidated yet.
Methods: We have established Reference intervals for amniotic fluid chitotriosidase using control amniotic fluids (n = 47) and compared the activity with amniotic fluids affected by lysosomal storage disorders (n = 25). Read More
Nat Commun 2018 09 10;9(1):3671. Epub 2018 Sep 10.
Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA.
Niemann-Pick type C disease is a fatal, progressive neurodegenerative disorder caused by loss-of-function mutations in NPC1, a multipass transmembrane glycoprotein essential for intracellular lipid trafficking. We sought to define the cellular machinery controlling degradation of the most common disease-causing mutant, I1061T NPC1. We show that this mutant is degraded, in part, by the proteasome following MARCH6-dependent ERAD. Read More
J Nat Prod 2018 Sep 6;81(9):2018-2025. Epub 2018 Sep 6.
Department of Chemistry and Biochemistry , University of Notre Dame , Notre Dame , Indiana 46556 , United States.
We report the first evidence of GEX1A, a polyketide known to modulate alternative pre-mRNA splicing, as a potential treatment for Niemann-Pick type C disease. GEX1A was isolated from its producing organism, Streptomyces chromofuscus, and screened in NPC1 mutant cells alongside several semisynthetic analogues. We found that GEX1A and analogues are capable of restoring cholesterol trafficking in NPC1 mutant fibroblasts, as well as altering the expression of NPC1 isoforms detected by Western blot. Read More
JIMD Rep 2018 Sep 6. Epub 2018 Sep 6.
Department of Neurodegenerative Diseases and Gerontopsychiatry/Neurology, University Hospital Bonn, Bonn, Germany.
Niemann-Pick type C disease (NPC) is a neurovisceral lysosomal storage disorder with a heterogeneous phenotype including ataxia, cognitive impairment, impairment of vertical saccades, and psychiatric symptoms, among many others. Based on clinical, genetic, and biomarker findings, recent guidelines put forward a screening for atypical and oligosymptomatic forms of NPC in clinical niches with an increased risk. Here, we report methods and results of a negative screening study in the niche of a memory clinic. Read More
Proteins 2018 Nov 22;86(11):1165-1175. Epub 2018 Oct 22.
Department of Microbiology, University of Tennessee, Knoxville, Tennessee.
The Niemann-Pick type C1 (NPC1) protein is a large transmembrane protein located in lysosomes/endosomes. NPC1 binds cholesterol (CLR) and transports it to cellular membrane and endoplasmic reticulum. Mutations in NPC1 cause Niemann-Pick type C (NPC) disease, a rare autosomal disorder characterized by intracellular accumulations of CLR and subsequent neurodegeneration leading to premature death. Read More
Int J Mol Sci 2018 Sep 4;19(9). Epub 2018 Sep 4.
Department of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
The Niemann Pick type C (NPC) proteins, NPC1 and NPC2, are involved in the lysosomal storage disease, NPC disease. The formation of a NPC1⁻NPC2 protein⁻protein complex is believed to be necessary for the transfer of cholesterol and lipids out of the late endosomal (LE)/lysosomal (Lys) compartments. Mutations in either NPC1 or NPC2 can lead to an accumulation of cholesterol and lipids in the LE/Lys, the primary phenotype of the NPC disease. Read More
Mol Genet Metab 2018 Aug 24. Epub 2018 Aug 24.
Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:
Background: Niemann-Pick disease type C1 (NPC1) is a rare, neurodegenerative cholesterol storage disorder. Diagnostic delay of >5 years is common due to the rarity of the disease and non-specific early symptoms. To improve diagnosis and facilitate early intervention, we previously developed a newborn screening assay based on newly identified plasma bile acid biomarkers. Read More
Front Integr Neurosci 2018 14;12:35. Epub 2018 Aug 14.
Institute of Anatomy, Rostock University Medical Center, Rostock, Germany.
Neurodegenerative diseases are often accompanied by olfactory deficits. Here we use a rare neurovisceral lipid storage disorder, Niemann-Pick disease C1 (NPC1), to illustrate disease-specific dynamics of olfactory dysfunction and its reaction upon therapy. Previous findings in a transgenic mouse model ( showed severe morphological and electrophysiological alterations of the olfactory epithelium (OE) and the olfactory bulb (OB) that ameliorated under therapy with combined 2-hydroxypropyl-ß-cyclodextrin (HPßCD)/allopregnanolone/miglustat or HPßCD alone. Read More
Sci Rep 2018 Aug 28;8(1):12981. Epub 2018 Aug 28.
State Key Laboratory of Rice Biology; Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Ministry of Agriculture; Institute of Insect Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Cyrtorhinus lividipennis Reuter (Hemiptera: Miridae) is an important egg predator of planthoppers which are destructive rice pests. The chemosensory genes in the mirid antennae play important roles in mating and prey-seeking behaviors. To gain a better understanding of the olfaction of C. Read More
Clin Chim Acta 2018 Nov 25;486:387-394. Epub 2018 Aug 25.
Clinical Division and Research Unit of Metabolic Diseases, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy. Electronic address:
Background: Although representing two distinct disease entities, Niemann-Pick disease type C (NP-C) disease and acid sphingomyelinase deficiency (ASMD) share several phenotypic features. The lack of biomarkers was responsible in the past of diagnostic delay. Recently, plasma oxysterols, cholestan-3β,5α,6β-triol (Triol) and 7-ketocholesterol (7-KC) and lysosphingolipids, Lyso-sphingomyelin (Lyso-SM) and Lysosphingomyelin-509 (Lyso-SM-509), have been proposed as diagnostic biomarkers. Read More
Methods Mol Biol 2018 ;1836:139-158
Institute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany.
Our understanding of infection biology is based on experiments in which pathogen or host proteins are perturbed by small compound inhibitors, mutation, or depletion. This approach has been remarkably successful, as, for example, demonstrated by the independent identification of the endosomal membrane protein Niemann-Pick C1 as an essential factor for Ebola virus infection in both small compound and insertional mutagenesis screens (Côté, Nature 477:344-348, 2011; Carette et al., Nature 477:340-343, 2011). Read More
Dis Model Mech 2018 08 15;11(9). Epub 2018 Aug 15.
Section on Molecular Dysmorphology, Division of Translational Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA
Niemann-Pick disease type C1 (NPC1) is a rare autosomal recessive lysosomal storage disease primarily caused by mutations in NPC1 is characterized by abnormal accumulation of unesterified cholesterol and glycolipids in late endosomes and lysosomes. Common signs include neonatal jaundice, hepatosplenomegaly, cerebellar ataxia, seizures and cognitive decline. Both mouse and feline models of NPC1 mimic the disease progression in humans and have been used in preclinical studies of 2-hydroxypropyl-β-cyclodextrin (2HPβCD; VTS-270), a drug that appeared to slow neurological progression in a Phase 1/2 clinical trial. Read More
Nucleic Acid Ther 2018 Oct 22;28(5):273-284. Epub 2018 Aug 22.
1 Massachusetts General Hospital Cancer Center , Charlestown, Massachusetts.
The Ebola virus is a zoonotic pathogen that can cause severe hemorrhagic fever in humans, with up to 90% lethality. The deadly 2014 Ebola outbreak quickly made an unprecedented impact on human lives. While several vaccines and therapeutics are under development, current approaches contain several limitations, such as virus mutational escape, need for formulation or refrigeration, poor scalability, long lead-time, and high cost. Read More
Int J Biol Sci 2018 23;14(10):1175-1185. Epub 2018 Jun 23.
Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Cholesterol plays a key role in membrane protein function and signaling in endothelial cells. Thus, disturbing cholesterol trafficking is an effective approach for inhibiting angiogenesis. We recently identified astemizole (AST), an antihistamine drug, as a cholesterol trafficking inhibitor from a phenotypic screen. Read More
BMC Neurol 2018 Aug 17;18(1):117. Epub 2018 Aug 17.
Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, 187-8551, Kodaira, Tokyo, Japan.
Background: Niemann-Pick disease type C (NPC) is a lysosomal storage disorder with severe prognosis. Disease-specific therapy is crucial to prevent disease progression; however, diagnosing NPC is quite difficult because of remarkably variable clinical presentations. The NPC Suspicion Index (NPC-SI) was developed to overcome this problem. Read More
Orphanet J Rare Dis 2018 Aug 16;13(1):143. Epub 2018 Aug 16.
Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK.
Background: Niemann-Pick disease type C (NPC) is a lysosomal storage disease with a heterogeneous neurodegenerative clinical course. Multiple therapies are in clinical trials and inclusion criteria are currently mainly based on age and neurological signs, not taking into consideration differential individual rates of disease progression.
Results: In this study, we have evaluated a simple metric, denoted annual severity increment score (ASIS), that measures rate of disease progression and could easily be used in clinical practice. Read More
Orphanet J Rare Dis 2018 Aug 15;13(1):140. Epub 2018 Aug 15.
Mayo Clinic, Rochester, MN, USA.
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. Read More
Genet Med 2018 Aug 10. Epub 2018 Aug 10.
Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
Purpose: We conducted a consented pilot newborn screening (NBS) for Pompe, Gaucher, Niemann-Pick A/B, Fabry, and MPS 1 to assess the suitability of these lysosomal storage disorders (LSDs) for public health mandated screening.
Methods: At five participating high-birth rate, ethnically diverse New York City hospitals, recruiters discussed the study with postpartum parents and documented verbal consent. Screening on consented samples was performed using multiplexed tandem mass spectrometry. Read More
Sci China Life Sci 2018 Oct 7;61(10):1222-1232. Epub 2018 Aug 7.
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, the Institute for Advanced Studies, Wuhan University, Wuhan, 430072, China.
Niemann-Pick type C2 (NPC2) is a lysosome luminal protein that functions in concert with NPC1 to mediate egress of low-density lipoprotein-derived cholesterol from lysosome. The nuclear factor kappa B subunit 2 (NF-κB2) protein is a component of NF-κB transcription factor complex critically implicated in immune and inflammatory responses. Here, we report that NF-κB2 regulates intracellular cholesterol transport by controlling NPC2 expression. Read More
Eur J Pediatr 2018 Nov 31;177(11):1609-1615. Epub 2018 Jul 31.
Pediatric Metabolic Clinic, Pediatric Division, Soroka Medical Center, Ben-Gurion University, Beersheba, Israel.
Niemann-Pick disease type C (NPC) is a lysosomal storage disorder caused by mutations in either NPC-1 or NPC-2 genes, resulting in abnormal intracellular cholesterol trafficking. The estimated prevalence of NPC disease is 1: 120,000-150,000. Lung involvement has been described in only few patients with NPC, mostly NPC2. Read More