DOCSLIB.ORG

WO 2016/164762 Al 13 October 2016 (13.10.2016) P O P C T

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2016/164762 Al 13 October 2016 (13.10.2016) P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/164762 Al 13 October 2016 (13.10.2016) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07K 14/705 (2006.01) C12N 15/11 (2006.01) kind of national protection available): AE, AG, AL, AM, C12N 15/09 (2006.01) C12N 15/12 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) International Application Number: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US20 16/026703 HN, HR, HU, ID, IL, ΓΝ , IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, 8 April 2016 (08.04.2016) MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (25) Filing Language: English SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (26) Publication Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 62/144,895 8 April 2015 (08.04.2015) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (71) Applicant: MODERNA THERAPEUTICS, INC. TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, [US/US]; 200 Technology Square, Cambridge, Massachu TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, setts 02139 (US). DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, (72) Inventors: ELLSWORTH, Jeff Lynn; 23 Meriam Street, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, Lexington, Massachusetts 02420 (US). BOLEN, Joseph GW, KM, ML, MR, NE, SN, TD, TG). Beene; 1 Avery Street, 29B, Boston, Massachusetts 021 11 (US). GREGOIRE, Francine M.; 184 Austin Street SI, Published: Newton, Massachusetts 02465 (US). GUILD, Justin; 495 — with international search report (Art. 21(3)) Edgell Rd, Framingham, Massachusetts 01701 (US). — with sequence listing part of description (Rule 5.2(a)) (74) Agents: NANNENGA-COMBS, Bonnie et al; Sterne Kessler Goldstein & Fox P.L.L.C, 1100 New York Aven ue, N.W., Washington, District of Columbia 20005 (US). (54) Title: POLYNUCLEOTIDES ENCODING LOW DENSITY LIPOPROTEIN RECEPTOR EGF-A AND INTRACELLULAR DOMAIN MUTANTS AND METHODS OF USING THE SAME II O FIG. 2 0 (57) Abstract: The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynuc leotide molecules encoding low density lipoprotein receptor comprising least one amino acid mutation in the EGF-A domain and at least one or a single amino acid mutation in the intracellular domain. POLYNUCLEOTIDES ENCODING LOW DENSITY LIPOPROTEIN RECEPTOR EGF-A AND INTRACELLULAR DOMAIN MUTANTS AND METHODS OF USING THE SAME REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY VIA EFS-WEB [0001] The content of the electronically submitted sequence listing (Name: 3529_021PC01_SeqListing_ST25.txt"; Size: 2,607,509 bytes; and date of creation: April 07, 2016) filed herewith the application is incorporated by reference in its entirety. BACKGROUND OF THE INVENTION [0002] High cholesterol is one of a number of risk factors for heart attack and stroke. Although poor diet and lack of excise are common causes of high cholesterol, genetic changes can also influence cholesterol levels. For example, familiar hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels in the blood, specifically very high levels of low-density lipoprotein (LDL). FH also leads to early cardiovascular disease. [0003] Cholesterol targeting drugs on the market include statins, fibrates, niacin, bile acid sequestrants (resins), phytosterols, or other compounds that prevent absorption of fats, reduce absorption of cholesterol, or target genes in the cholesterol trafficking pathway. Cholesterol lowering drugs approved for the treatment of homozygous FH include mipomersen, an antisense oligonucleotide inhibitor which targets ApoB-100, and lomitapide, an inhibitor of the microsomal triglyceride transfer protein (MTP or MTTP) which is necessary for very low-density lipoprotein (VLDL) assembly and secretion in the liver. [0004] Not all cholesterol targeting drugs can adequately lower LDL levels, particularly in FH patients. Liver related problems are commonly associated with cholesterol targeting drugs, particularly elevation in serum transaminases and accumulation of hepatic fat (or hepatic steatosis) have been reported. In addition, there are risks and contraindications associated with certain conditions or other medications. SUMMARY OF THE INVENTION [0005] Certain aspects of the invention are directed to a polynucleotide comprising an open reading frame of linked nucleosides encoding a human low density lipoprotein receptor (LDLR) or functional fragment thereof comprising at least one amino acid mutation in the EGF-A domain and at least one or a single amino acid mutation in the intracellular domain, wherein the at least one amino acid mutation in the EGF-A domain abrogates binding of PCSK9 to the LDLR or functional fragment thereof, and wherein the open reading frame is optionally codon-optimized. [0006] Another aspect of the invention is directed to a polynucleotide comprising an open reading frame of linked nucleosides encoding a human low density lipoprotein receptor (LDLR) or functional fragment thereof comprising at least one amino acid mutation in the EGF-A domain and at least one amino acid mutation in the intracellular domain, wherein the at least one amino acid mutation in the EGF-A domain abrogates binding of PCSK9 to the LDLR or functional fragment thereof and, optionally, at least one of the amino acids corresponding to K830 or C839 of human LDLR is intact, and wherein the open reading frame is optionally codon-optimized. [0007] In some embodiments, the at least one mutation in the EGF-A domain is at an amino acid residue corresponding to N316, L339, or the combination of N316 and L339 of human LDLR (SEQ ID NO:43). [0008] In some embodiments, the at least one mutation in the EGF-A domain comprises a deletion of the amino acid, an insertion of at least one amino acid, a conservative substitution, or a substitution. [0009] In some embodiments, the at least one mutation in the EGF-A domain is a substitution from the N (asparagine) corresponding to amino acid residue 316 of SEQ ID NO:43 to an amino acid selected from the group consisting of glycine, alanine, valine, leucine, and isoleucine. [0010] In some embodiments, the at least one mutation in the EGF-A domain is a substitution from the L (leucine) corresponding to amino acid residue 339 of SEQ ID NO:43 to an amino acid selected from the group consisting of aspartate, glutamate, glutamine, and asparagine. [0011] In some embodiments, the single mutation or at least one mutation in the intracellular domain is at an amino acid residue corresponding to K816, K830, or C839 of human LDLR (SEQ ID NO:43). [0012] In some embodiments, the single mutation or at least one mutation in the intracellular domain comprises a deletion of the amino acid, an insertion of at least one amino acid, a conservative substitution, or a substitution. [0013] In some embodiments, the single mutation or at least one mutation in the intracellular domain is a substitution from the K (lysine) corresponding to an amino acid residue 816 or 830 of SEQ ID NO:43 to an amino acid selected from the group consisting of histidine or arginine. [0014] In some embodiments, the single mutation or at least one mutation in the intracellular domain is a substitution from the C (cysteine) corresponding to an amino acid residue 839 of SEQ ID NO:43 to an amino acid selected from the group consisting of glycine, alanine, valine, leucine, and isoleucine. [0015] In some embodiments, the LDLR or functional fragment thereof comprises one mutation in the EGF-A domain and one mutation in the intracellular domain. [0016] In some embodiments, the one mutation in the EGF-A domain corresponds to N316A of human LDLR and the one mutation in the intracellular domain corresponds to K830R of human LDLR. [0017] In some embodiments, the polynucleotide comprises at least one chemically modified nucleoside. In some embodiments, the at least one chemically modified nucleoside is selected from any of those listed in Table 5. In some embodiments, the at least one chemically modified nucleoside is selected from the group consisting of pseudouridine, Nl-methylpseudouridine, 5- methylcytosine, 5-methoxyuridine, and a combination thereof. In some embodiments, the nucleosides in the open reading frame are chemically modified by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 9 5% , at least 99%, or 100%. In some embodiments, the chemically modified nucleosides in the open reading frame are selected from the group consisting of uridine, adenine, cytosine, guanine, and any combination thereof. [0018] In some embodiments, the uridine nucleosides in the open reading frame are chemically modified by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99%, or 100%. [0019] In some embodiments, the adenine nucleosides in the open reading frame are chemically modified by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99%, or 100%.
Load more

Recommended publications
  • Lysosomal Acid Lipase Deficiency Lipid Insights December 9, 2013
    Lysosomal Acid Lipase Deficiency Lipid Insights December 9, 2013 Daniel J. Rader, MD LAL Deficiency . History . Pathophysiology and genetic epidemiology . Liver disease . Dyslipidemia and atherosclerosis . Diagnostic considerations . Therapeutic considerations . Summary Biology of Lysosomal Acid Lipase LDL particle lysosome Free cholesterol and free fatty acids nucleus Hepatocyte Lysosomal Acid Lipase (LAL) Deficiency: A single disease, with marked clinical heterogeneity LAL Deficiency is sometimes called: . Wolman disease (infantile presentation with growth failure) . Cholesteryl Ester Storage Disease or CESD (LAL deficiency presentation in children and adults) . Acid Cholesteryl Ester Hydrolase Deficiency, Type 2 . Acid Lipase Disease . Cholesteryl Ester Hydrolase Deficiency Storage Disease . LIPA Deficiency LAL Deficiency . History . Pathophysiology and genetic epidemiology . Liver disease . Dyslipidemia and atherosclerosis . Diagnostic considerations . Therapeutic considerations . Summary A brief history: The first phenotypic descriptions . Abramov, Shorr, and Wolman, 1956: “Generalized xanthomatosis with calcified adrenals” (“Wolman” disease) . Fredrickson, 1963: “Cholesterol ester storage disease” – “…likely a specific hepatic defect in cholesterol ester metabolism.” . Patrick and Lake : “Deficiency of an acid lipase in Wolman’s disease”, Nature, 1969 . Burke and Schubert : “Deficient activity of hepatic acid lipase in cholesterol ester storage disease”, Science, 1972 . Cortner et al: “Genetic variation of lysosomal acid lipase”, Pediatric Research, 1976 . Goldstein, et al: “Role of lysosomal acid lipase in the metabolism of plasma Low density lipoprotein,” JBC, 1975 . Anderson, et al: Cloning of the lysosomal acid lipase cDNA, JBC, 1991 . Anderson, et al: Mutations at the lysosomal acid cholesterol esterase gene locus in Wolman disease. Proc Natl Acad Sci USA, 1994 . Klima H, et al: “A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease.” J Clin Invest, 1993.
    [Show full text]
  • Pharmacy Medical Necessity Guidelines: Kanuma™ (Sebelipase Alfa) Effective: April 13, 2021
    Pharmacy Medical Necessity Guidelines: Kanuma™ (sebelipase alfa) Effective: April 13, 2021 Prior Authorization Required √ Type of Review – Care Management Not Covered Type of Review – Clinical Review √ PRECERT Pharmacy (RX) or Medical (MED) Benefit MED Department to Review /MM These pharmacy medical necessity guidelines apply to the following: Fax Numbers: Commercial Products Tufts Health Plan Commercial products – large group plans Commercial Products: Tufts Health Plan Commercial products – small group and individual plans PRECERT: 617.972.9409 Tufts Health Freedom Plan products – large group plans Tufts Health Freedom Plan products – small group plans Tufts Health Public • CareLinkSM – Refer to CareLink Procedures, Services and Items Requiring Prior Authorization Plans Products: MM: 888.415.9055 Tufts Health Public Plans Products Tufts Health Direct – A Massachusetts Qualified Health Plan (QHP) (a commercial product) Tufts Health Together – MassHealth MCO Plan and Accountable Care Partnership Plans Tufts Health RITogether – A Rhode Island Medicaid Plan Note: This guideline does not apply to Medicare Members (includes dual eligible Members). OVERVIEW FOOD AND DRUG ADMINISTRATION-APPROVED INDICATIONS Kanuma (sebelipase) is a hydrolytic lysosomal cholesteryl ester and triacylglycerol-specific enzyme indicated for the treatment of patients with a diagnosis of Lysosomal Acid Lipase (LAL) deficiency. Lysosomal Acid Lipase deficiency is an autosomal recessive lysosomal storage disorder characterized by a genetic defect (mutation in the LIPA gene) resulting in a marked decrease or loss in activity of the LAL enzyme. The primary site of action of the LAL enzyme is the lysoso me, where the enzyme normally causes the breakdown of lipid particles. Deficient LAL enzyme activity results in progressive complications due to the lysosomal accumulation of cholesteryl esters and triglycerides in multiple organs, including the liver, spleen, intestine, and the walls of blood vessels.
    [Show full text]
  • Kanuma (Sebelipase Alfa) Original Effective Date: 11/21/2016 04/24 Policy Number: MCP-289 Revision Date(S)
    Subject: Kanuma (sebelipase alfa) Original Effective Date: 11/21/2016 04/24 Policy Number: MCP-289 Revision Date(s): Review Date(s): 12/15/2016; 9/19/2017, 9/13/2018 MCPC Approval Date: 9/13/2018 DISCLAIMER This Molina Clinical Policy (MCP) is intended to facilitate the Utilization Management process. It expresses Molina's determination as to whether certain services or supplies are medically necessary, experimental, investigational, or cosmetic for purposes of determining appropriateness of payment. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that this service or supply is covered (i.e., will be paid for by Molina) for a particular member. The member's benefit plan determines coverage. Each benefit plan defines which services are covered, which are excluded, and which are subject to dollar caps or other limits. Members and their providers will need to consult the member's benefit plan to determine if there are any exclusion(s) or other benefit limitations applicable to this service or supply. If there is a discrepancy between this policy and a member's plan of benefits, the benefits plan will govern. In addition, coverage may be mandated by applicable legal requirements of a State, the Federal government or CMS for Medicare and Medicaid members. CMS's Coverage Database can be found on the CMS website. The coverage directive(s) and criteria from an existing National Coverage Determination (NCD) or Local Coverage Determination (LCD) will supersede the contents of this MCP document and provide the directive for all Medicare members.
    [Show full text]
  • ICD-9-CM C&M March 2011 Diagnosis Agenda
    ICD-10 Coordination and Maintenance Committee Meeting September 22-23, 2015 Diagnosis Agenda Welcome and announcements Donna Pickett, MPH, RHIA Co-Chair, ICD-10 Coordination and Maintenance Committee Diagnosis Topics: Contents Abscess of Anal and Rectal Regions .............................................................................. 12 Cheryl Bullock Garth H. Utter, MD MSc Patient Assessment and Outcome Committee Outcome of the American Association for the Surgery of Trauma Acquired Hydrocephalus ................................................................................................ 15 Donna Pickett Amblyopia Suspect ........................................................................................................ 16 Shannon McConnell Lamptey Michael X Repka, M.D., MBA Medical Director of Government Affairs American Academy of Ophthalmology Professor of Ophthalmology and Pediatrics Johns Hopkins University School of Medicine Amyotrophic Lateral Sclerosis (ALS) .......................................................................... 17\ Donna Pickett Asthma Control Status: Controlled and Uncontrolled .................................................... 18 Cheryl Bullock Elizabeth Matsu, MD, MHS American Academy of Allergy Asthma and Immunology (AAAAI) Professor of Pediatrics, Epidemiology, and Environmental Health Sciences at Johns Hopkins University Atrial Fibrillation ........................................................................................................... 20 David Berglund, MD Chronic hepatitis
    [Show full text]
  • WO 2015/051214 Al 9 April 2015 (09.04.2015) W P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/051214 Al 9 April 2015 (09.04.2015) W P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07K 14/705 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/US20 14/058967 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 3 October 2014 (03. 10.2014) KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (25) Filing Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (26) Publication Language: English SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/886,137 3 October 201 3 (03. 10.2013) US (84) Designated States (unless otherwise indicated, for every 61/903,485 13 November 2013 (13. 11.2013) US kind of regional protection available): ARIPO (BW, GH, 61/952,906 14 March 2014 (14.03.2014) us GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/052,139 18 September 2014 (18.09.2014) us TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: MODERNA THERAPEUTICS, INC.
    [Show full text]
  • Health and Medicine Volume 4
    The Eyes iii THE FACTS ON FILE ENCYCLOPEDIA OF HEALTH AND MEDICINE IN FOUR VOLUMES: VOLUME 4 An Amaranth Book iv The Eyes To your health! The information presented in The Facts On File Encyclopedia of Health and Medicine is provided for research purposes only and is not intended to replace consultation with or diagnosis and treatment by medical doctors or other qualified experts. Readers who may be experiencing a condition or disease described herein should seek medical attention and not rely on the information found here as medical advice. The Facts On File Encyclopedia of Health and Medicine in Four Volumes: Volume 4 Copyright © 2007 by Amaranth Illuminare All rights reserved. No part of this book may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage or retrieval systems, without permission in writing from the publisher. For information contact: Facts On File, Inc. An imprint of Infobase Publishing 132 West 31st Street New York NY 10001 Produced by Amaranth Illuminare PO Box 573 Port Townsend WA 98368 Library of Congress Cataloging-in-Publication Data The Facts on File encyclopedia of health and medicine / Amaranth Illuminare and Deborah S. Romaine. p. ; cm. “An Amaranth book.” Includes index. ISBN 0-8160-6063-0 (hc : alk. paper) 1. Medicine—Encyclopedias. 2. Health—Encyclopedias. [DNLM: 1. Medicine—Encyclopedias—English. 2. Physiological Processes—Encyclopedias—English. WB 13 R842f 2006] I. Title: Encyclopedia of health and medicine. II. Romaine, Deborah S., 1956- III. Facts on File, Inc. IV. Title. R125.R68 2006 610.3—dc22 2005027679 Facts On File books are available at special discounts when purchased in bulk quantities for businesses, associations, institutions, or sales promotions.
    [Show full text]
  • ICD-9-CM C&M March 2011 Diagnosis Agenda
    ICD-10 Coordination and Maintenance Committee Meeting September 22-23, 2015 Diagnosis Agenda Welcome and announcements Donna Pickett, MPH, RHIA Co-Chair, ICD-10 Coordination and Maintenance Committee Diagnosis Topics: Contents Abscess of Anal and Rectal Regions ............................................................................... 12 Cheryl Bullock Garth H. Utter, MD MSc Patient Assessment and Outcome Committee Outcome of the American Association for the Surgery of Trauma Acquired Hydrocephalus ................................................................................................. 15 Donna Pickett Amblyopia Suspect .......................................................................................................... 16 Shannon McConnell Lamptey Michael X Repka, M.D., MBA Medical Director of Government Affairs American Academy of Ophthalmology Professor of Ophthalmology and Pediatrics Johns Hopkins University School of Medicine Amyotrophic Lateral Sclerosis (ALS) ............................................................................ 17\ Donna Pickett Asthma Control Status: Controlled and Uncontrolled ..................................................... 18 Cheryl Bullock Elizabeth Matsu, MD, MHS American Academy of Allergy Asthma and Immunology (AAAAI) Professor of Pediatrics, Epidemiology, and Environmental Health Sciences at Johns Hopkins University Atrial Fibrillation ............................................................................................................. 20 David Berglund, MD Chronic
    [Show full text]
  • Universidade Federal De Santa Catarina Centro De Ciências Da Saúde Programa De Pós-Graduação Em Ciências Médicas
    UNIVERSIDADE FEDERAL DE SANTA CATARINA CENTRO DE CIÊNCIAS DA SAÚDE PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS MÉDICAS CAMILA DA ROSA WITECK Características clínicas e laboratoriais de pacientes pediátricos com deficiência de lipase ácida: Scoping Review. Florianópolis 2021 CAMILA DA ROSA WITECK Características clínicas e laboratoriais de pacientes pediátricos com deficiência de lipase ácida: Scoping Review. Dissertação submetida ao Programa de Ciências Médicas da Universidade Federal de Santa Catarina para a obtenção do título de mestre em ciências médicas Orientadora: Profa. Dra. Maria Marlene de Souza Pires Florianópolis 2021 CAMILA DA ROSA WITECK Características clinicas e laboratoriais de pacientes pediátricos com deficiência de lipase ácida : Scoping Review. O presente trabalho em nível de mestrado foi avaliado e aprovado por banca examinadora composta pelos seguintes membros: Prof.(a)Maria Marlene de Souza Pires, Dr.(a) Universidade Federal de Santa Catarina Prof.(a) Suely Grosseman , Dr.(a) Universidade Federal de Santa Catarina Prof.(a) Priscyla Walesca Targino de Azevedo Simões, Dr.(a) Universidade Federal do ABC Certificamos que esta é a versão original e final do trabalho de conclusão que foi julgado adequado para obtenção do título de mestre em Ciências Médicas. ____________________________ Profa. Katia Lin, Dra. Coordenação do Programa de Pós-Graduação ____________________________ Profa. Maria Marlene de Souza Pires, Dra. Orientadora Florianópolis 2021 A toda minha família, a base sólida do meu crescimento pessoal e profissional. AGRADECIMENTOS À Dra. Maria Marlene de Souza Pires, orientadora deste trabalho, pela dedicação e apoio. Sua importância em minha vida acadêmica e pessoal iniciou-se na graduação de Medicina pelas brilhantes observações, competência no âmbito profissional e acadêmico.
    [Show full text]
  • ICD-10-CM C&M September Diagnosis Agenda
    ICD-10 Coordination and Maintenance Committee Meeting September 22-23, 2015 Diagnosis Agenda Welcome and announcements Donna Pickett, MPH, RHIA Co-Chair, ICD-10 Coordination and Maintenance Committee Diagnosis Topics: Contents Abscess of Anal and Rectal Regions ............................................................................... 12 Cheryl Bullock Garth H. Utter, MD MSc Patient Assessment and Outcome Committee Outcome of the American Association for the Surgery of Trauma Acquired Hydrocephalus ................................................................................................. 15 Donna Pickett Amblyopia Suspect .......................................................................................................... 16 Shannon McConnell Lamptey Michael X Repka, M.D., MBA Medical Director of Government Affairs American Academy of Ophthalmology Professor of Ophthalmology and Pediatrics Johns Hopkins University School of Medicine Amyotrophic Lateral Sclerosis (ALS) ............................................................................. 17 Donna Pickett Asthma Control Status: Controlled and Uncontrolled ..................................................... 18 Cheryl Bullock Elizabeth Matsu, MD, MHS American Academy of Allergy Asthma and Immunology (AAAAI) Professor of Pediatrics, Epidemiology, and Environmental Health Sciences at Johns Hopkins University Atrial Fibrillation ............................................................................................................. 20 David Berglund, MD Chronic
    [Show full text]
  • Vol. 19, No. 2, 2018 Make.Pmd
    J MEDICINE 2018; 19: 130-132 Cholesteryl Ester Storage Disease – A Rare Presentation MADHABI KARMAKER,1 SARMIN AKTER,2 AHMEDUL KABIR,3 KHAN ABUL KALAM AZAD,4 ABID HOSSAIN MOLLAH5 Abstract: Cholesteryl Ester Storage Disease (CESD) is a rare genetic disease characterized by accumulation of cholesteryl esters and triglycerides in many tissues due to deficiency of Lysosomal Acid Lipase (LAL/ LIPA) enzyme, which is essential for hydrolysis of triglycerides and cholesterol esters in lysosomes.1 The diagnosis is indicated by abnormal lipid profile, deposition of cholesterol crystals in internal organs and reduced acid lipase activity in leukocytes. Here we report a 16 year-old girl who presented with repeated episodes of hepatic encephalopathy with onset of first symptom at 9 years of age with history of consanguinity of marriage between parents. On examination, we found hepatosplenomegaly. Laboratory examination showed abnormal lipid profile and reduced activity of acid lipase enzyme in leukocytes. After exclusion of other possible pathological conditions and on the basis of lab criteria, we diagnose the case as Cholesteryl Ester Storage Disease (CESD). KKKeeeywords: Cholesteryl Ester Storage Disease (CESD), cholesteryl esters, triglycerides, Lysosomal Acid Lipase. DOI: http://dx.doi.org/10.3329/jom.v19i2.37235 Introduction: symptoms and may go undiagnosed until adulthood. CESD CESD is inherited as an autosomal recessive condition 1 So is characterized by alterations of blood lipoprotein profile; parents who are close relatives (consanguineous) have a patients present with hypercholesterolemia, higher chance to have children with a recessive genetic hypertriglyceridaemia, HDL deficiency with abnormal lipid disorder. CESD affects males and females in equal numbers.2 deposition in many organs.
    [Show full text]
  • Kasenra Sebelipase Alfa MCP289
    Subject: Kanuma (sebelipase alfa) Original Effective Date: 11/21/2016 Policy Number: MCP-289 Revision Date(s): Review Date(s): DISCLAIMER This Molina Clinical Policy (MCP) is intended to facilitate the Utilization Management process. It expresses Molina's determination as to whether certain services or supplies are medically necessary, experimental, investigational, or cosmetic for purposes of determining appropriateness of payment. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that this service or supply is covered (i.e., will be paid for by Molina) for a particular member. The member's benefit plan determines coverage. Each benefit plan defines which services are covered, which are excluded, and which are subject to dollar caps or other limits. Members and their providers will need to consult the member's benefit plan to determine if there are any exclusion(s) or other benefit limitations applicable to this service or supply. If there is a discrepancy between this policy and a member's plan of benefits, the benefits plan will govern. In addition, coverage may be mandated by applicable legal requirements of a State, the Federal government or CMS for Medicare and Medicaid members. CMS's Coverage Database can be found on the CMS website. The coverage directive(s) and criteria from an existing National Coverage Determination (NCD) or Local Coverage Determination (LCD) will supersede the contents of this MCP document and provide the directive for all Medicare members. SUMMARY OF EVIDENCE/POSITION This policy addresses the coverage of Kanuma (sebelipase alfa), a hydrolytic lysosomal cholesteryl ester and triacylglycerol-specific enzyme administered intravenously for the treatment of the rare disease lysosomal acid lipase deficiency (LAL-D), also known as Wolman disease (WD) and cholesteryl ester storage disease (CESD).
    [Show full text]