keyword
MENU ▼
Read by QxMD icon Read
search

Gaucher disease

keyword
https://www.readbyqxmd.com/read/28319420/modelling-long-term-evolution-of-chitotriosidase-in-non-neuronopathic-gaucher-disease
#1
Cristina Drugan, Tudor C Drugan, Paula Grigorescu-Sido, Ioana Naşcu
Chitotriosidase, an enzyme secreted by activated macrophages, is widely used as a biomarker for therapeutic monitoring and patient follow-up in Gaucher disease (GD), a lysosomal disorder caused by an inherited deficiency of glucocerebrosidase. We analyzed the long-term evolution of chitotriosidase aiming to establish an accurate model that describes the influence of enzyme replacement therapy (ERT) and the impact of several covariates. A total of 55 patients with non-neuronopathic (type 1) GD were followed for almost 17 years (during a maximum of 7...
March 20, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28302345/newborn-screening-for-six-lysosomal-storage-disorders-in-a-cohort-of-mexican-patients-three-year-findings-from-a-screening-program-in-a-closed-mexican-health-system
#2
Juana Inés Navarrete-Martínez, Ana Elena Limón-Rojas, Maria de Jesús Gaytán-García, Jesús Reyna-Figueroa, Guillermo Wakida-Kusunoki, Ma Del Rocío Delgado-Calvillo, Consuelo Cantú-Reyna, Héctor Cruz-Camino, David Eduardo Cervantes-Barragán
OBJECTIVE: To evaluate the results of a lysosomal newborn screening (NBS) program in a cohort of 20,018 Mexican patients over the course of 3years in a closed Mexican Health System (Petróleos Mexicanos [PEMEX] Health Services). STUDY DESIGN: Using dried blood spots (DBS), we performed a multiplex tandem mass spectrometry enzymatic assay for six lysosomal storage disorders (LSDs) including Pompe disease, Fabry disease, Gaucher disease, mucopolysaccharidosis type I (MPS-I), Niemann-Pick type A/B, and Krabbe disease...
March 9, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28295625/oral-ambroxol-increases-brain-glucocerebrosidase-activity-in-a-nonhuman-primate
#3
Anna Migdalska-Richards, Wai Kin D Ko, Qin Li, Erwan Bezard, Anthony H V Schapira
Mutations in the glucocerebrosidase 1 (GBA1) gene are related to both Parkinson disease (PD) and Gaucher disease (GD). In both cases, the condition is associated with deficiency of glucocerebrosidase (GCase), the enzyme encoded by GBA1. Ambroxol is a small molecule chaperone that has been shown in mice to cross the blood-brain barrier, increase GCase activity and reduce alpha-synuclein protein levels. In this study, we analyze the effect of ambroxol treatment on GCase activity in healthy nonhuman primates. We show that daily administration of ambroxol results in increased brain GCase activity...
March 12, 2017: Synapse
https://www.readbyqxmd.com/read/28286087/minos-insertion-mutant-of-the-drosophila-gba-gene-homologue-showed-abnormal-phenotypes-of-climbing-ability-sleep-and-life-span-with-accumulation-of-hydroxy-glucocerebroside
#4
Haruhisa Kawasaki, Takahiro Suzuki, Kumpei Ito, Tsubasa Takahara, Naoko Goto-Inoue, Mitsutoshi Setou, Kazuki Sakata, Norio Ishida
Gaucher's disease in humans is considered a deficiency of glucocerebrosidase (GlcCerase) that result in the accumulation of its substrate, glucocerebroside (GlcCer). Although mouse models of Gaucher's disease have been reported from several laboratories, these models are limited due to the perinatal lethality of GlcCerase gene. Here, we examined phenotypes of Drosophila melanogaster homologues genes of the human Gaucher's disease gene by using Minos insertion. One of two Minos insertion mutants to unknown function gene (CG31414) accumulates the hydroxy-GlcCer in whole body of Drosophila melanogaster...
March 7, 2017: Gene
https://www.readbyqxmd.com/read/28274788/management-goals-for-type-1-gaucher-disease-an-expert-consensus-document-from-the-european-working-group-on-gaucher-disease
#5
M Biegstraaten, T M Cox, N Belmatoug, M G Berger, T Collin-Histed, S Vom Dahl, M Di Rocco, C Fraga, F Giona, P Giraldo, M Hasanhodzic, D A Hughes, P O Iversen, A I Kiewiet, E Lukina, M Machaczka, T Marinakis, E Mengel, G M Pastores, U Plöckinger, H Rosenbaum, C Serratrice, A Symeonidis, J Szer, J Timmerman, A Tylki-Szymańska, M Weisz Hubshman, D I Zafeiriou, A Zimran, C E M Hollak
Gaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions [obtained by patient- reported outcome measurements (PROMs)] is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed...
October 24, 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28272068/rare-disease-heralded-by-pulmonary-manifestations-avoiding-pitfalls-of-an-asthma-label
#6
S Bajaj, M Muranjan, S Karande, D Prabhat
Pulmonary manifestations are seldom recognized as symptoms of storage disorders. The report describes the diagnostic journey in a 30-month-old male infant, born of a third-degree consanguineous marriage referred to our institute as severe persistent asthma. History revealed that the child had progressively worsening breathlessness and persistent dry cough not associated with fever but accompanied by weight loss. On physical examination, there was growth failure, respiratory distress, clubbing, hepatosplenomegaly, and occasional rhonchi...
March 3, 2017: Journal of Postgraduate Medicine
https://www.readbyqxmd.com/read/28270550/papers-of-note-in-nature543-7643
#7
Annalisa M VanHook
This week's articles describe a cause of chronic inflammation in Gaucher disease, a method for improving the efficacy of T cell-mediated cancer immunotherapy, a type of oncogene amplification that enhances tumor heterogeneity, and a mechanism whereby mechanical stress maintains epithelial homeostasis.
March 7, 2017: Science Signaling
https://www.readbyqxmd.com/read/28268595/modeling-non-clinical-and-clinical-drug-tests-in-gaucher-disease
#8
Clyde F Phelix, Allen K Bourdon, Greg Villareal, Richard G LeBaron
There is need for modeling biological systems to accelerate drug pipelines for treating metabolic diseases. The eliglustat treatment for Gaucher disease is approved by the FDA with a companion genomic test. The Transcriptome-To-Metabolome™ biosimulation technology was used to model, in silico, a standard non-clinical eliglustat test with an in vitro canine kidney cell system over-expressing a human gene; and a clinical test using human fibroblasts from control and Gaucher disease subjects. Protein homology modeling and docking studies were included to gather affinity parameters for the kinetic metabolic model...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28265599/screening-methods-for-identifying-pharmacological-chaperones
#9
REVIEW
Min Hyeon Shin, Hyun-Suk Lim
Protein folding is crucial for most proteins to achieve their correct three-dimensional conformations and function properly. Defects in protein folding frequently caused by mutations lead to a range of protein misfolding diseases, including Alzheimer's disease, Parkinson's disease, cystic fibrosis, amyloidosis, Gaucher disease, etc. One approach to treat these devastating diseases would be to use pharmacological chaperones, which are small-molecules that bind to and stabilize misfolded proteins, thereby correcting their pathogenic misfolding and rescuing their functions...
March 7, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28263001/assessment-of-bone-health-in-patients-with-type-1-gaucher-disease-using-impact-microindentation
#10
Sabina Herrera, Jordi Pérez-López, Marc Moltó-Abad, Roberto Güerri-Fernández, Elena Cabezudo, Silvana Novelli, Jordi Esteve, Albert Hernández, Inmaculada Roig, Xavier Solanich, Daniel Prieto-Alhambra, Xavier Nogués, Adolfo Díez-Pérez
BACKGROUND: Gaucher disease (GD), one of the commonest lysosomal disorders (a global population incidence of 1:50,000), is characterized by beta-glucocerebrosidase deficiency. Some studies have demonstrated bone infiltration in up to 80% of patients, even if asymptomatic. Bone disorder remains the main cause of morbidity in these patients, along with osteoporosis, avascular necrosis, and bone infarcts. Enzyme replacement therapy (ERT) has been shown to improve these symptoms. METHODS: This cross-sectional study included patients with type 1 Gaucher disease (GD1) selected from the Catalan Study Group on GD...
March 6, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28258214/identification-of-a-feedback-loop-involving-beta-glucosidase-2-and-its-product-sphingosine-sheds-light-on-the-molecular-mechanisms-in-gaucher-disease
#11
Sophie Schonauer, Heinz G Körschen, Anke Penno, Andreas Rennhack, Bernadette Breiden, Konrad Sandhoff, Katharina Gutbrod, Peter Dörmann, Diana N Raju, Per Haberkant, Mathias J Gerl, Britta Brügger, Hila Zigdon, Ayelet Vardi, Anthony H Futerman, Christoph Thiele, Dagmar Wachten
The lysosomal acid beta-glucosidase GBA1 and the non-lysosomal beta-glucosidase GBA2 degrade glucosylceramide (GlcCer) to glucose and ceramide in different cellular compartments. Loss of GBA2 activity and the resulting accumulation of GlcCer results in male infertility, whereas mutations in the GBA1 gene and loss of GBA1 activity cause the lipid-storage disorder Gaucher disease. However, the role of GBA2 in Gaucher disease pathology and its relationship to GBA1 is not well understood. Here, we report a GBA1-dependent down-regulation of GBA2 activity in patients with Gaucher disease...
March 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28242126/type-1-gaucher-disease-cyp2d6-eliglustat
#12
Laurent Becquemont
Type 1 Gaucher disease is a rare genetic disease characterized by enzymatic deficit leading to glucosylceramide overload in body tissues (lysosomal overload disease). Standard treatment is based on substitutive enzyme therapy by intravenous perfusion. A new drug for oral administration, eliglustat, was recently awarded marketing approval in Europe and the USA. Eliglustat acts by reducing the enzyme substrate. Eliglustat is mainly eliminated by a CYP2D6 pathway. CYP2D6 exhibits genetic variability or expression, leading to 20-fold differences in serum levels...
January 30, 2017: Thérapie
https://www.readbyqxmd.com/read/28231462/the-complicated-relationship-between-gaucher-disease-and-parkinsonism-insights-from-a-rare-disease
#13
REVIEW
Elma Aflaki, Wendy Westbroek, Ellen Sidransky
The discovery of a link between mutations in GBA1, encoding the lysosomal enzyme glucocerebrosidase, and the synucleinopathies directly resulted from the clinical recognition of patients with Gaucher disease with parkinsonism. Mutations in GBA1 are now the most common known genetic risk factor for several Lewy body disorders, and an inverse relationship exists between levels of glucocerebrosidase and oligomeric α-synuclein. While the underlying mechanisms are still debated, this complicated association is shedding light on the role of lysosomes in neurodegenerative disorders, demonstrating how insights from a rare disorder can direct research into the pathogenesis and therapy of seemingly unrelated common diseases...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28226774/modeling-non-clinical-and-clinical-drug-tests-in-gaucher-disease
#14
Clyde F Phelix, Allen K Bourdon, Greg Villareal, Richard G LeBaron, Clyde F Phelix, Allen K Bourdon, Greg Villareal, Richard G LeBaron, Richard G LeBaron, Clyde F Phelix, Allen K Bourdon, Greg Villareal
There is need for modeling biological systems to accelerate drug pipelines for treating metabolic diseases. The eliglustat treatment for Gaucher disease is approved by the FDA with a companion genomic test. The Transcriptome-To-Metabolome™ biosimulation technology was used to model, in silico, a standard non-clinical eliglustat test with an in vitro canine kidney cell system over-expressing a human gene; and a clinical test using human fibroblasts from control and Gaucher disease subjects. Protein homology modeling and docking studies were included to gather affinity parameters for the kinetic metabolic model...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225753/complement-drives-glucosylceramide-accumulation-and-tissue-inflammation-in-gaucher-disease
#15
Manoj K Pandey, Thomas A Burrow, Reena Rani, Lisa J Martin, David Witte, Kenneth D Setchell, Mary A Mckay, Albert F Magnusen, Wujuan Zhang, Benjamin Liou, Jörg Köhl, Gregory A Grabowski
Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Here we show that activation of complement C5a and C5a receptor 1 (C5aR1) controls GC accumulation and the inflammatory response in experimental and clinical Gaucher disease...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28224082/clinical-characteristics-of-adult-patients-with-inborn-errors-of-metabolism-in-spain-a-review-of-500-cases-from-university-hospitals
#16
J Pérez-López, L Ceberio-Hualde, J S García-Morillo, J M Grau-Junyent, A Hermida Ameijeiras, M López-Rodríguez, J C Milisenda, M Moltó Abad, M Morales-Conejo, J J Nava Mateos
Patients with inborn errors of metabolism (IEMs) have become an emerging and challenging group in the adult healthcare system whose needs should be known in order to implement appropriate policies and to adapt adult clinical departments. We aimed to analyze the clinical characteristics of adult patients with IEMs who attend the most important Spanish hospitals caring for these conditions. A cohort study was conducted in 500 patients, categorized by metabolic subtype according to pathophysiological classification...
March 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28223512/glucosylceramide-synthase-inhibition-alleviates-aberrations-in-synucleinopathy-models
#17
S Pablo Sardi, Catherine Viel, Jennifer Clarke, Christopher M Treleaven, Amy M Richards, Hyejung Park, Maureen A Olszewski, James C Dodge, John Marshall, Elina Makino, Bing Wang, Richard L Sidman, Seng H Cheng, Lamya S Shihabuddin
Mutations in the glucocerebrosidase gene (GBA) confer a heightened risk of developing Parkinson's disease (PD) and other synucleinopathies, resulting in a lower age of onset and exacerbating disease progression. However, the precise mechanisms by which mutations in GBA increase PD risk and accelerate its progression remain unclear. Here, we investigated the merits of glucosylceramide synthase (GCS) inhibition as a potential treatment for synucleinopathies. Two murine models of synucleinopathy (a Gaucher-related synucleinopathy model, Gba(D409V/D409V) and a A53T-α-synuclein overexpressing model harboring wild-type alleles of GBA, A53T-SNCA mouse model) were exposed to a brain-penetrant GCS inhibitor, GZ667161...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28219443/a-new-framework-for-evaluating-the-health-impacts-of-treatment-for-gaucher-disease-type-1
#18
Michael L Ganz, Sean Stern, Alex Ward, Luba Nalysnyk, Martin Selzer, Alaa Hamed, Neal Weinreb
BACKGROUND: The Disease Severity Scoring System (DS3) is a validated measure for evaluating Gaucher disease type 1 (GD1) severity. We developed a new framework, consisting of health states, transition probabilities between those states, and preferences for those states (utilities) based on the DS3 to predict long-term outcomes of patients starting treatment. We defined nine mutually exclusive (alive) health states based on three DS3 categories: mild (0 ≤ DS3 ≤ 3.5) without symptoms of bone disease; mild with bone pain, mild with severe skeletal complications (SSC) defined as lytic lesions, avascular necrosis, or fracture; moderate (3...
February 20, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28218669/a-review-of-gaucher-disease-pathophysiology-clinical-presentation-and-treatments
#19
REVIEW
Jérôme Stirnemann, Nadia Belmatoug, Fabrice Camou, Christine Serratrice, Roseline Froissart, Catherine Caillaud, Thierry Levade, Leonardo Astudillo, Jacques Serratrice, Anaïs Brassier, Christian Rose, Thierry Billette de Villemeur, Marc G Berger
Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207759/investigations-on-therapeutic-glucocerebrosidases-through-paired-detection-with-fluorescent-activity-based-probes
#20
Wouter W Kallemeijn, Saskia Scheij, Sascha Hoogendoorn, Martin D Witte, Daniela Herrera Moro Chao, Cindy P A A van Roomen, Roelof Ottenhoff, Herman S Overkleeft, Rolf G Boot, Johannes M F G Aerts
Deficiency of glucocerebrosidase (GBA) causes Gaucher disease (GD). In the common non-neuronopathic GD type I variant, glucosylceramide accumulates primarily in the lysosomes of visceral macrophages. Supplementing storage cells with lacking enzyme is accomplished via chronic intravenous administration of recombinant GBA containing mannose-terminated N-linked glycans, mediating the selective uptake by macrophages expressing mannose-binding lectin(s). Two recombinant GBA preparations with distinct N-linked glycans are registered in Europe for treatment of type I GD: imiglucerase (Genzyme), contains predominantly Man(3) glycans, and velaglucerase (Shire PLC) Man(9) glycans...
2017: PloS One
keyword
keyword
64776
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"