DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 8,232,073 B2 Crawford Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 8,232,073 B2 Crawford Et Al US008232073B2 (12) United States Patent (10) Patent No.: US 8,232,073 B2 Crawford et al. (45) Date of Patent: Jul. 31, 2012 (54) QUANTIFICATION OF NON-REDUCING END FOREIGN PATENT DOCUMENTS GLYCAN RESIDUAL COMPOUNDS WO WO-01-31045 A1 5, 2001 WO WO-01-36977 A2 5, 2001 Inventors: Brett E. Crawford, Poway, CA (US); WO WO-03-092601 A1 11 2003 (75) WO WO-03-106997 A1 12/2003 Jillian R. Brown, Poway, CA (US); WO WO-2004-01904.0 A1 3, 2004 Charles A. Glass, San Diego, CA (US); WO WO-2007-01.0089 A2 1, 2007 Jim R. Beitel, San Diego, CA (US); WO WO-2010-078514 A2 T 2010 Robin M. Jackman, San Diego, CA OTHER PUBLICATIONS (US) An et al., “Glucose tetrasaccharide as a biomarker for monitoring the (73) Assignee: Zacharon Pharmaceuticals, Inc., San therapeutic response to enzyme replacement therapy for Pompe dis ease. Mol Gen Metabol 85:247-254, 2005. Diego, CA (US) An et al., “Profiling of glycans in serum for the discovery of potential biomarkers for ovarian cancer.” JProteome Res. 5(7): 1626-35, 2006. (*) Notice: Subject to any disclaimer, the term of this Deakin et al., “A simplified and sensitive fluorescent method for patent is extended or adjusted under 35 disaccharide analysis of both heparin Sulfate and chondroitin U.S.C. 154(b) by 473 days. dermatan sulfates from biological samples.” Glycobiology 18:483 491 (2008). Deegan et al., "Clinical evaluation of chemokine and enzymatic (21) Appl. No.: 12/649,110 biomarkers of Gaucher disease.” Blood Cells Mol Dis35(2): 259-67. 2005. (22) Filed: Dec. 29, 2009 Fuller et al., “Glycosaminoglycan degradation fragments in mucopolysaccharidosis I.” Glycobiology 14(5):443-50, 2004. (65) Prior Publication Data Hansen et al., “HPLC glycosaminoglycan analysis in patients with Graves’ disease.” Clin Sci92:51 1-517 (1997). US 2010/O173337 A1 Jul. 8, 2010 Kirmiz et al., “A serum glycomics approach to breast cancer biomarkers.” Mol Cell Proteomics 6(1):43-55, 2007. Related U.S. Application Data Maccari et al., “Anomolous Structure of Urinary Glycosaminoglycans in Patients with Pseudoxanthoma Elasticum.” (60) Provisional application No. 61/142.291, filed on Jan. Clin Chem 49:380-388 (2003). 2, 2009, provisional application No. 61/164.365, filed Mason et al., "Characterization of Sulfated oligosaccharides in mucopolysaccharidosis type IIIA by electrospray ionization mass on Mar. 27, 2009, provisional application No. spectrometry.” Anal Chem 78(13):4534-42, 2006. 61/238,079, filed on Aug. 28, 2009. Toma et al., “Differences in the nonreducing ends of heparan Sulfates excreted by patients with mucopolysaccharidoses revealed by bacte (51) Int. C. rial heparitinases: a new tool for structural studies and differential CI2O I/34 (2006.01) diagnosis of Sanfilippo's and Hunter's syndromes.” Lab Invest CI2O I/48 (2006.01) 75(6):771-81, 1996. PCT/US2009/069944 International Search Report mailed Aug. 31, (52) U.S. Cl. ............................................ 435/15; 435/18 2010. (58) Field of Classification Search .................... 435/15, GB 0922711.7 Examination Report dated Dec. 2, 2010. 435/18 See application file for complete search history. Primary Examiner — Herbert J Lilling (74) Attorney, Agent, or Firm — Wilson, Sonsini, (56) References Cited Goodrich & Rosati U.S. PATENT DOCUMENTS (57) ABSTRACT 6,936,424 B1 8/2005 Watkins et al. Provided herein are methods of diagnosing or monitoring the 7,651,847 B2 1/2010 Lebrilla et al. 2002.0102737 A1 8/2002 Millington et al. treatment of abnormal glycan accumulation or a disorder 2003, OO24012 A1 1/2003 Abdennebi-Najar et al. associated with abnormal glycan accumulation. 2006/0269974 A1 11/2006 Dwek et al. 2007, 0161074 A1 7/2007 Tomatsu et al. 15 Claims, 4 Drawing Sheets U.S. Patent Jul. 31, 2012 Sheet 1 of 4 US 8,232,073 B2 U.S. Patent Jul. 31, 2012 Sheet 2 of 4 US 8,232,073 B2 s v799 - C e6C s s s s s s s s U.S. Patent Jul. 31, 2012 Sheet 3 of 4 US 8,232,073 B2 s Z899 - ( e^O s s s s s s U.S. Patent Jul. 31, 2012 Sheet 4 of 4 US 8,232,073 B2 6699 - (9/O US 8,232,073 B2 1. 2 QUANTIFICATION OF NON-REDUCING END Provided in certain embodiments herein is a method of GLYCAN RESIDUAL COMPOUNDS diagnosing an individual as having a disease or condition associated with abnormal glycan biosynthesis, degradation, CROSS-REFERENCE or accumulation, the method comprising: 5 a. transforming a glycan of a biological sample with a This application claims the benefit of U.S. Provisional glycan degradation enzyme to liberate a glycan residual Application No. 61/142.291, filed 2 Jan. 2009, U.S. Provi compound from the non-reducing end of the glycan; sional Application No. 61/164.365, filed 27 Mar. 2009, and b. measuring the amount of the glycan residual compound U.S. Provisional Application No. 61/238,079, filed 28 Aug. liberated by the functioning glycan degradation enzyme 2009, which applications are incorporated herein by refer 10 with an analytical device; and CCC. c. determining whether the amount of liberated glycan residue is abnormal. BACKGROUND OF THE INVENTION In some embodiments, provided herein is a method of monitoring the treatment of a disorder associated with the Many human diseases are caused by or correlated with 15 abnormal degradation, biosynthesis and/or accumulation of changes in glycosylation. In order to use these changes as glycans, the method comprising: biomarkers of disease, analytical methods are used to quan a. following administration of an agent for treating a dis tify the changes. The published methods use antibodies, chro order associated with the abnormal degradation, biosyn matography and/or mass spectrometry techniques to resolve thesis and/or accumulation of glycans to an individual in and quantify the intact or partially intact glycans. These meth need thereof, using an analytical instrument to measure ods are challenging due to the complexity and number of the amount of a population of a biomarker comprising a possible glycan structures present in biological samples. In a non-reducing end glycan residual compounds present in single disease state there can be thousands of different novel a transformed biological sample, the biomarker being glycan structures that are present; however, each on their own generated by treating a population of glycans, in or is a weak marker of disease. 25 isolated from a biological sample from the individual, with at least one digesting glycan enzyme(s), wherein SUMMARY OF THE INVENTION prior to enzyme treatment, the biomarker is not present in abundance in Samples from individuals with the dis Described herein are populations of glycans that are trans ease or condition relative to individuals without the dis formed into populations of biomarkers using glycan degra 30 ease or condition, and dation enzymes. Further described herein are the use of ana b. determining whether or not the amount of the amount of lytical instruments to characterize the population of biomarker has decreased or increased at a slower rate biomakers (i.e., non-reducing end glycan residual com compared to the amount or rate of increase prior to pounds, such as monosaccharides) in order to provide rel administration of the agent for treating a disorder asso evant information about the population of biomarkers, the 35 ciated with the abnormal degradation, biosynthesis and/ population of biomarkers and the biological sample that pro or accumulation of glycans. vided the population of biomarkers. In some embodiments, the abnormal glycan accumulation Provided in certain embodiments herein are methods of or disorder associated therewith is caused by an abnormally detecting glycan accumulation and/or abnormal glycan bio functioning glycan degradation enzyme and wherein the synthesis and/or degradation in a biological sample, the 40 abnormally functioning glycan degradation enzyme and gly method comprising: can degradation enzyme are of the same type (e.g., the glycan a. transforming a glycan of a biological sample with a degradation utilized in the transformation process is a func glycan degradation enzyme to liberate a glycan residual tioning glycan degradation enzyme whereas the abnormally compound from the non-reducing end of the glycan; functioning enzyme is not, such as due to deletions, inser b. measuring the amount of the glycan residual compound 45 tions, Substitutions, or other modifications to the enzyme liberated by the functioning glycan degradation enzyme sequence). In certain embodiments, the abnormally function with an analytical device. ing glycan degradation enzyme functions abnormally as a In some embodiments, a method described herein com result of being present in an abnormally low amount, func prises a method of diagnosing an individual as having a dis tioning improperly, or a combination thereof. In some ease or condition associated with abnormal glycan biosyn 50 embodiments, the abnormal glycan accumulation comprises thesis, degradation, or accumulation, the method comprising: the accumulation of abnormal amounts of glycans. In certain a. generating a biomarker comprising of one or more non embodiments, the abnormal glycan accumulation comprises reducing end glycan residual compound, wherein the the accumulation of abnormal amounts of normal glycans. In biomarker is generated by treating a population of gly Some embodiments, the abnormal glycan accumulation com cans, in or isolated from a biological sample from the 55 prises the accumulation of abnormal amounts of abnormal individual, with at least one digesting glycan enzymes, glycans. wherein prior to enzyme treatment, the biomarker is not In certain embodiments, the biomarker is not present in the present in abundance in Samples from individuals with original biological sample. In some embodiments, the biom the disease or condition relative to individuals without arker is not present in the biological sample after isolating a the disease or condition, and 60 population of glycans therefrom (e.g., prior to transformation b.
Load more

Recommended publications
  • Bacteria Belonging to Pseudomonas Typographi Sp. Nov. from the Bark Beetle Ips Typographus Have Genomic Potential to Aid in the Host Ecology
    insects Article Bacteria Belonging to Pseudomonas typographi sp. nov. from the Bark Beetle Ips typographus Have Genomic Potential to Aid in the Host Ecology Ezequiel Peral-Aranega 1,2 , Zaki Saati-Santamaría 1,2 , Miroslav Kolaˇrik 3,4, Raúl Rivas 1,2,5 and Paula García-Fraile 1,2,4,5,* 1 Microbiology and Genetics Department, University of Salamanca, 37007 Salamanca, Spain; [email protected] (E.P.-A.); [email protected] (Z.S.-S.); [email protected] (R.R.) 2 Spanish-Portuguese Institute for Agricultural Research (CIALE), 37185 Salamanca, Spain 3 Department of Botany, Faculty of Science, Charles University, Benátská 2, 128 01 Prague, Czech Republic; [email protected] 4 Laboratory of Fungal Genetics and Metabolism, Institute of Microbiology of the Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic 5 Associated Research Unit of Plant-Microorganism Interaction, University of Salamanca-IRNASA-CSIC, 37008 Salamanca, Spain * Correspondence: [email protected] Received: 4 July 2020; Accepted: 1 September 2020; Published: 3 September 2020 Simple Summary: European Bark Beetle (Ips typographus) is a pest that affects dead and weakened spruce trees. Under certain environmental conditions, it has massive outbreaks, resulting in attacks of healthy trees, becoming a forest pest. It has been proposed that the bark beetle’s microbiome plays a key role in the insect’s ecology, providing nutrients, inhibiting pathogens, and degrading tree defense compounds, among other probable traits. During a study of bacterial associates from I. typographus, we isolated three strains identified as Pseudomonas from different beetle life stages. In this work, we aimed to reveal the taxonomic status of these bacterial strains and to sequence and annotate their genomes to mine possible traits related to a role within the bark beetle holobiont.
    [Show full text]
  • Epidemiology of Mucopolysaccharidoses Update
    diagnostics Review Epidemiology of Mucopolysaccharidoses Update Betul Celik 1,2 , Saori C. Tomatsu 2 , Shunji Tomatsu 1 and Shaukat A. Khan 1,* 1 Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA; [email protected] (B.C.); [email protected] (S.T.) 2 Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA; [email protected] * Correspondence: [email protected]; Tel.: +302-298-7335; Fax: +302-651-6888 Abstract: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by a lysosomal enzyme deficiency or malfunction, which leads to the accumulation of glycosaminoglycans in tissues and organs. If not treated at an early stage, patients have various health problems, affecting their quality of life and life-span. Two therapeutic options for MPS are widely used in practice: enzyme replacement therapy and hematopoietic stem cell transplantation. However, early diagnosis of MPS is crucial, as treatment may be too late to reverse or ameliorate the disease progress. It has been noted that the prevalence of MPS and each subtype varies based on geographic regions and/or ethnic background. Each type of MPS is caused by a wide range of the mutational spectrum, mainly missense mutations. Some mutations were derived from the common founder effect. In the previous study, Khan et al. 2018 have reported the epidemiology of MPS from 22 countries and 16 regions. In this study, we aimed to update the prevalence of MPS across the world. We have collected and investigated 189 publications related to the prevalence of MPS via PubMed as of December 2020. In total, data from 33 countries and 23 regions were compiled and analyzed.
    [Show full text]
  • Hexosaminidase in Mast Β Primary Role of Degranulation Indicator in Mast Cells?
    Does β-Hexosaminidase Function Only as a Degranulation Indicator in Mast Cells? The Primary Role of β-Hexosaminidase in Mast Cell Granules This information is current as of September 25, 2021. Nobuyuki Fukuishi, Shinya Murakami, Akane Ohno, Naoya Yamanaka, Nobuaki Matsui, Kenji Fukutsuji, Sakuo Yamada, Kouji Itoh and Masaaki Akagi J Immunol 2014; 193:1886-1894; Prepublished online 11 July 2014; Downloaded from doi: 10.4049/jimmunol.1302520 http://www.jimmunol.org/content/193/4/1886 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2014/07/11/jimmunol.130252 Material 0.DCSupplemental References This article cites 52 articles, 18 of which you can access for free at: http://www.jimmunol.org/content/193/4/1886.full#ref-list-1 Why The JI? Submit online. by guest on September 25, 2021 • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2014 by The American Association of
    [Show full text]
  • Quality Assessment Enzyme Analysis for Lysosomal Storage Diseases ERNDIM / EUGT Meeting 5-6 October 2006, Prague
    QQuality Assessment Enzyme Analysis for Lysosomal Storage Diseases ERNDIM / EUGT meeting 5-6 October 2006, Prague Results of 1st “large scale” pilot Quality Assessment Enzyme Analysis for Lysosomal Storage Diseases Laboratories Rotterdam Hamburg/Heidelberg Dr, Zoltan Lukacs/Dr. Friederike Bürger QA-pilot for LSD’s the aims • Inter-laboratory variation ─ Many participants: > 30 • Intra-laboratory variation ─ Analyse two pairs of identical control samples (blind) • Proficiency testing of enzyme deficiencies ─ Which samples are best? - Blood samples: most widely used, but impractible - Fibroblasts: good but laborious - EBV lymphoblasts: easy to obtain, not widely used QA-pilot for LSD’s the set up • Samples, without clinical information ─ Leukocytes ─ EBV lymphoblasts ─ Fibroblasts • Enzymes: easy ones ─ 4MU-substrates ─ Simple colorimetric assays • Shipping: economic ─ Send at room temp., postal service - Lyophilised enzymes, stable at room temp. for 5 days - Fibroblasts • Data entry through existing ERNDIM programmes ─ “Metabolite presentation” (www.erndimqa.nl Æ Lysosomal Enzymes) QA-pilot for LSD’s the participants • Questionnaire to members (85 from 21 countries) ─ 40 labs want to join a QA-pilot ─ 65% want to include DBS in future QA-schemes • Samples sent, data returned ─ 40 labs received samples ─ 36 labs entered data on www.erndimqa.nl QA-pilot for LSD’s the samples • 10 samples ─ 4 leukocytes (two duplicate samples) ─ 4 EBV lymphoblasts ─ 2 fibroblasts • 10 easy enzymes ─ specific enzyme activity (e.g.. nmol/h/mg) ─ normalise to
    [Show full text]
  • Uptake of -(L)-Iduronidase Produced by Retrovirally Transduced
    Gene Therapy (1997) 4, 63–75 1997 Stockton Press All rights reserved 0969-7128/97 $12.00 Uptake of a-(L)-iduronidase produced by retrovirally transduced fibroblasts into neuronal and glial cells in vitro K Stewart1, OA Brown1, AE Morelli1, LJ Fairbairn2, LS Lashford2,3, A Cooper4, CE Hatton4, TM Dexter2, MG Castro1 and PR Lowenstein1 1Molecular Medicine Unit, Department of Medicine, University of Manchester School of Medicine; 2CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester; 3Academic Unit of Pediatric Oncology, Christie Hospital NHS Trust, Manchester; and 4Willink Biochemical Genetics Unit, Royal Manchester Children’s Hospital, Manchester, UK The uptake of recombinant a-(L)-iduronidase into glial and higher in actively dividing or immature brain cells. Conse- neuronal cells, produced by retrovirally transduced NIH3T3 quently, (1) neuronal metabolism ought to be capable of fibroblasts, was studied. We demonstrate that: (1) neuronal cross correction by enzyme provided by genetically engine- and glial cells take up a-(L)-iduronidase released into the ered and transplanted cells provided by bone marrow medium by retrovirally transduced fibroblasts expressing transplantation (BMT); (2) that BMT could have a more high levels of a-(L)-iduronidase; (2) both glial and neuronal beneficial effect on neurological function if performed as cells express the cation independent mannose-6-phos- early as possible; and (3) given that the uptake mechanism phate receptor responsible for lysosomal enzyme uptake; of glial cells has a higher capacity, it might be easier to and (3) uptake of the lysosomal enzyme can be blocked target diseases like the leukodystrophies in which lysoso- by excess free mannose-6-phosphate, but not glucose-6- mal enzymes are needed in glial cells, compared to dis- phosphate.
    [Show full text]
  • Functional Characterization of Carbohydrate-Active Enzymes from Marine Bacteria
    Functional characterization of carbohydrate-active enzymes from marine bacteria I n a u g u r a l d i s s e r t a t i o n zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) der Mathematisch-Naturwissenschaftlichen Fakultät der Universität Greifswald vorgelegt von Marcus Bäumgen Greifswald, 28.02.2020 Dekan: Prof. Dr. Werner Weitschies 1. Gutachter: Prof. Dr. Uwe T. Bornscheuer 2. Gutachter: Prof. Dr. Harry Brumer Tag der Promotion: 24.06.2020 II III Wissenschaft ist das Werkzeug, welches es uns ermöglicht, das große Puzzel der Natur und des Lebens zu lösen. IV Auch wenn wir den Weg des Wissens und der Weisheit niemals bis zum Ende beschreiten können, so ist doch jeder Schritt, den wir tun, ein Schritt in eine bessere Welt. V Content Abbreviations ..................................................................................................................... IX 1. Introduction ..................................................................................................................... 1 1.1 The marine carbon cycle .............................................................................................. 1 1.1.1 Algal blooms .......................................................................................................... 1 1.1.2 The marine carbohydrates ulvan and xylan ........................................................... 2 1.1.3 Marine polysaccharide utilization ........................................................................... 4 1.2 Carbohydrate-active enzymes
    [Show full text]
  • United States Patent (19) 11 Patent Number: 5,981,835 Austin-Phillips Et Al
    USOO598.1835A United States Patent (19) 11 Patent Number: 5,981,835 Austin-Phillips et al. (45) Date of Patent: Nov. 9, 1999 54) TRANSGENIC PLANTS AS AN Brown and Atanassov (1985), Role of genetic background in ALTERNATIVE SOURCE OF Somatic embryogenesis in Medicago. Plant Cell Tissue LIGNOCELLULOSC-DEGRADING Organ Culture 4:107-114. ENZYMES Carrer et al. (1993), Kanamycin resistance as a Selectable marker for plastid transformation in tobacco. Mol. Gen. 75 Inventors: Sandra Austin-Phillips; Richard R. Genet. 241:49-56. Burgess, both of Madison; Thomas L. Castillo et al. (1994), Rapid production of fertile transgenic German, Hollandale; Thomas plants of Rye. Bio/Technology 12:1366–1371. Ziegelhoffer, Madison, all of Wis. Comai et al. (1990), Novel and useful properties of a chimeric plant promoter combining CaMV 35S and MAS 73 Assignee: Wisconsin Alumni Research elements. Plant Mol. Biol. 15:373-381. Foundation, Madison, Wis. Coughlan, M.P. (1988), Staining Techniques for the Detec tion of the Individual Components of Cellulolytic Enzyme 21 Appl. No.: 08/883,495 Systems. Methods in Enzymology 160:135-144. de Castro Silva Filho et al. (1996), Mitochondrial and 22 Filed: Jun. 26, 1997 chloroplast targeting Sequences in tandem modify protein import specificity in plant organelles. Plant Mol. Biol. Related U.S. Application Data 30:769-78O. 60 Provisional application No. 60/028,718, Oct. 17, 1996. Divne et al. (1994), The three-dimensional crystal structure 51 Int. Cl. ............................. C12N 15/82; C12N 5/04; of the catalytic core of cellobiohydrolase I from Tricho AO1H 5/00 derma reesei. Science 265:524-528.
    [Show full text]
  • The Metabolism of Tay-Sachs Ganglioside: Catabolic Studies with Lysosomal Enzymes from Normal and Tay-Sachs Brain Tissue
    The Metabolism of Tay-Sachs Ganglioside: Catabolic Studies with Lysosomal Enzymes from Normal and Tay-Sachs Brain Tissue JOHN F. TALLMAN, WILLIAM G. JOHNSON, and ROSCOE 0. BRADY From the Developmental and Metabolic Neurology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20014, and the Department of Biochemistry, Georgetown University School of Medicine, Washington, D. C. 20007 A B S T R A C T The catabolism of Tay-Sachs ganglioside, date fronm the 19th century and over 599 cases have been N-acetylgalactosaminyl- (N-acetylneuraminosyl) -galac- reported (1). Onset of the disease is in the first 6 months tosylglucosylceramide, has been studied in lysosomal of life and is characterized by apathy, hyperacusis, motor preparations from normal human brain and brain ob- weakness, and appearance of a macular cherry-red spot tained at biopsy from Tay-Sachs patients. Utilizing Tay- in the retina. Seizures and progressive mental deteriora- Sachs ganglioside labeled with '4C in the N-acetylgalac- tion follow with blindness, deafness, and spasticity, lead- tosaminyl portion or 3H in the N-acetylneuraminosyl ing to a state of decerebrate rigidity. These infants usu- portion, the catabolism of Tay-Sachs ganglioside may be ally die by 3 yr of age (2). initiated by either the removal of the molecule of A change in the chemical composition of the brain of N-acetylgalactosamine or N-acetylneuraminic acid. The such patients was first detected by Klenk who showed activity of the N-acetylgalactosamine-cleaving enzyme that there was an increase in the ganglioside content (hexosaminidase) is drastically diminished in such compared with normal human brain tissue (3).
    [Show full text]
  • GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies
    International Journal of Molecular Sciences Review GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies Andrés Felipe Leal 1 , Eliana Benincore-Flórez 1, Daniela Solano-Galarza 1, Rafael Guillermo Garzón Jaramillo 1 , Olga Yaneth Echeverri-Peña 1, Diego A. Suarez 1,2, Carlos Javier Alméciga-Díaz 1,* and Angela Johana Espejo-Mojica 1,* 1 Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogotá 110231, Colombia; [email protected] (A.F.L.); [email protected] (E.B.-F.); [email protected] (D.S.-G.); [email protected] (R.G.G.J.); [email protected] (O.Y.E.-P.); [email protected] (D.A.S.) 2 Faculty of Medicine, Universidad Nacional de Colombia, Bogotá 110231, Colombia * Correspondence: [email protected] (C.J.A.-D.); [email protected] (A.J.E.-M.); Tel.: +57-1-3208320 (ext. 4140) (C.J.A.-D.); +57-1-3208320 (ext. 4099) (A.J.E.-M.) Received: 6 July 2020; Accepted: 7 August 2020; Published: 27 August 2020 Abstract: GM2 gangliosidoses are a group of pathologies characterized by GM2 ganglioside accumulation into the lysosome due to mutations on the genes encoding for the β-hexosaminidases subunits or the GM2 activator protein. Three GM2 gangliosidoses have been described: Tay–Sachs disease, Sandhoff disease, and the AB variant. Central nervous system dysfunction is the main characteristic of GM2 gangliosidoses patients that include neurodevelopment alterations, neuroinflammation, and neuronal apoptosis. Currently, there is not approved therapy for GM2 gangliosidoses, but different therapeutic strategies have been studied including hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, and gene therapy.
    [Show full text]
  • Identification of Potential Key Genes and Pathway Linked with Sporadic Creutzfeldt-Jakob Disease Based on Integrated Bioinformatics Analyses
    medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Sporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened.
    [Show full text]
  • Identification and Characterisation of Mucin Abnormalities in the Ganglionic Bowel in Hirschsprung’S Disease
    IDENTIFICATION AND CHARACTERISATION OF MUCIN ABNORMALITIES IN THE GANGLIONIC BOWEL IN HIRSCHSPRUNG’S DISEASE By Ruth Marian Speare Submitted for MD (Res) 1 Abstract Hirschsprung’s disease (HD) is a congenital abnormality of unknown origin, characterised by a lack of ganglion cells in the distal colon which results in functional colonic obstruction. The major cause of morbidity and mortality in these children results from an inflammatory condition called enterocolitis. Mucins are large glycoproteins produced by intestinal cells which are a vital part of the colonic defensive barrier to infection. Previous work has found that this barrier is deficient in children with HD in the aganglionic colon and in the immediately adjacent ganglionic colon and that this is related to the risk of developing enterocolitis. This study aimed to further investigate the mucin defensive barrier in a greater region of the ganglionic colon in HD, to establish the extent of any mucin deficiencies and whether these were confined to a limited region close to the aganglionic colon. Mucosal biopsies were collected at intervals along the colon at the time of corrective surgery or colostomy closure in the controls. Organ culture with radioactive mucin precursors was performed and the mucin produced was purified and analysed, results quantified by DNA content in the sample. Lectin binding studies were also carried out. Patients were found to produce lower levels of new mucins most distally, but much higher levels five centimetres proximal when compared to controls. The rest of the colon studied also showed changes in mucin production, with a lack of production of gel-forming mucins and sulphated secreted mucins in Hirschsprung’s disease higher up the colon.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,689,046 B2 Mayall Et Al
    USOO9689046B2 (12) United States Patent (10) Patent No.: US 9,689,046 B2 Mayall et al. (45) Date of Patent: Jun. 27, 2017 (54) SYSTEM AND METHODS FOR THE FOREIGN PATENT DOCUMENTS DETECTION OF MULTIPLE CHEMICAL WO O125472 A1 4/2001 COMPOUNDS WO O169245 A2 9, 2001 (71) Applicants: Robert Matthew Mayall, Calgary (CA); Emily Candice Hicks, Calgary OTHER PUBLICATIONS (CA); Margaret Mary-Flora Bebeselea, A. et al., “Electrochemical Degradation and Determina Renaud-Young, Calgary (CA); David tion of 4-Nitrophenol Using Multiple Pulsed Amperometry at Christopher Lloyd, Calgary (CA); Lisa Graphite Based Electrodes', Chem. Bull. “Politehnica” Univ. Kara Oberding, Calgary (CA); Iain (Timisoara), vol. 53(67), 1-2, 2008. Fraser Scotney George, Calgary (CA) Ben-Yoav. H. et al., “A whole cell electrochemical biosensor for water genotoxicity bio-detection”. Electrochimica Acta, 2009, 54(25), 6113-6118. (72) Inventors: Robert Matthew Mayall, Calgary Biran, I. et al., “On-line monitoring of gene expression'. Microbi (CA); Emily Candice Hicks, Calgary ology (Reading, England), 1999, 145 (Pt 8), 2129-2133. (CA); Margaret Mary-Flora Da Silva, P.S. et al., “Electrochemical Behavior of Hydroquinone Renaud-Young, Calgary (CA); David and Catechol at a Silsesquioxane-Modified Carbon Paste Elec trode'. J. Braz. Chem. Soc., vol. 24, No. 4, 695-699, 2013. Christopher Lloyd, Calgary (CA); Lisa Enache, T. A. & Oliveira-Brett, A. M., "Phenol and Para-Substituted Kara Oberding, Calgary (CA); Iain Phenols Electrochemical Oxidation Pathways”, Journal of Fraser Scotney George, Calgary (CA) Electroanalytical Chemistry, 2011, 1-35. Etesami, M. et al., “Electrooxidation of hydroquinone on simply prepared Au-Pt bimetallic nanoparticles'. Science China, Chem (73) Assignee: FREDSENSE TECHNOLOGIES istry, vol.
    [Show full text]