Cystic Fibrosis Update
|
|
- Kevin Fox
- 5 years ago
- Views:
Transcription
1 Cystic Fibrosis Update More than Decades of Discovery Dr. Raj Padman Professor of Pediatric TJU Board certified in Pediatrics, Pulmonology, and Sleep Medicine Dupont, Kosciusko Community, Lutheran, Rehabilitation, St. Joseph and The Orthopedic hospitals are owned in part by physicians.
2 Road Map History of Cystic Fibrosis The genetics of Cystic Fibrosis Clinical manifestation relating to pathophysiology Genotype to phenotype correlation Translational medicine as applied to Cystic Fibrosis
3 Cystic Fibrosis Most common serious autosomal recessive disease Highest incidence in people of northern European Extraction- 1/3, 300
4 Historical Aspects Carrier rate of 5% Cystic Fibrosis is not a new disease First described in 1930 Dupont, Kosciusko Community, Lutheran, Rehabilitation, St. Joseph and The Orthopedic hospitals are owned in part by physicians.
5 Reference In Early Folklore Literature Schmidt folk philosophy salty taste meant a child was bewitched 1800 Pfyffer-Dictionary of Swiss and German language If it tastes salty when someone is kissed on the brow, then this person is hexed. Dupont, Kosciusko Community, Lutheran, Rehabilitation, St. Joseph and The Orthopedic hospitals are owned in part by physicians.
6 Cystic Fibrosis Rokitansky earliest description of meconium ileus, perforation and peritonitis Fanconi published first paper on CF. Described two children with bronchiectasis and pancreatic insufficiency Anderson published first comprehensive description of 49 patients with CF of the pancreas. Related it to Coeliac Disease Dupont, Kosciusko Community, Lutheran, Rehabilitation, St. Joseph and The Orthopedic hospitals are owned in part by physicians.
7 Cystic Fibrosis Farber generalized disease of the exocrine glands with inspissation of mucous secreting gland mucoviscidosis DiSant Agnese demonstrated an abnormally high level of sodium chloride in sweat Dupont, Kosciusko Community, Lutheran, Rehabilitation, St. Joseph and The Orthopedic hospitals are owned in part by physicians.
8 Cystic Fibrosis African Americans 1/16, 800 Hispanics 1/9, 600 Asians 1/12, 000 Orientals in Hawaii 1/90, 00 Orientals in Great Britain 1/10, 000 Cases reported from Africa and Saudia Arabia Dupont, Kosciusko Community, Lutheran, Rehabilitation, St. Joseph and The Orthopedic hospitals are owned in part by physicians.
9
10
11
12
13
14
15
16
17 Survival CF Life Expectancy
18
19 Cystic Fibrosis Gene Isolated Lap Chi Tsui, Toronto Sick Children; Francis Collin-Ann Arbour, Michigan Chromosome 7q31; large size contain 27 exons; 250,000 base pairs >850 mutations identified 70% mutation deletion of three base pairs on tenth exon, loss of a single amino acid phenyl alanine at position 508 referred to as delta F508. Codes for cmp mediated chloride channel-cftr.
20 Site of CF Gene
21 F508 Mutation
22
23 Four Classes of CFTR Mutation Causing CF Class 1-defective protein production. Results from nonsense, frame shift due to insertions, deletions and splice site abnormalities Class II- defective processing. Most common CF mutation (delta F508) misfolded do not progress through biosynthetic pathway to cell membrane. Retained and degraded in endoplasmic reticulum Class III- defective regulation despite correct cellular localization, mutation in nucleotide binding domain. Channel opens less frequently. Abnormal response to ATP. Class IV- defective conduction, mutation in membrane spanning domain. Channel Correctly localized, normal regulation. Amount of concurrent is reduced.
24 Four Classes of CFTR Mutations Causing CF
25 Molecular Consequences of CFTR Mutations
26
27 Genotype Phenotype Relationships
28 Effectors of CFTR Phenotype
29 Mapping the CF Modifier Genes in Mouse
30 CFTR Mutations in Other Diseases Congenital bilateral absence of vas deferens (CBAVD) Obstructive Azoospermia Chronic Obstructive Pulmonary Disease (COPD) Diffused Bronchiectasis Allergic Broncopulmonary Aspergillosis Chronic Pseudomonas Bronchitis Chronic Bronchial Hypersecretion Chronic Sinusitis Pancreatitis Asthma
31
32 Cystic Fibrosis: Pathogenesis and New Therapies
33 Cystic Fibrosis Generalized Multi-Organ System disease from a single biochemical abnormality
34
35
36 Major Pathogenic Events in CF Lung Disease
37
38
39 Mucociliary Clearance And Obstruction Periciliary Liquid (PCL) CFTR normal Surface Epithelial Cells Tenacious Mucus cytoplasmic CFTR CF
40
41 Bronchoscopic Views of Normal and CF Airways
42 Domain Model of CFTR
43
44
45 What s New With CFTR? Intermolecular Interactions: CFTR is Linked to Binding Partners and Regulatory Networks!
46 Intermolecular Interactions Between the C-terminus of CFTR and Regulatory Network are Vital for CFTR Function!
47
48 Increased Sulfation of Mucins May Enhance Adherence of P aerugion
49 Incidence of Major Airway Pathogens by Patient Age
50
51 Neutrophil Phagocytosis
52 Release of Elastase and Oxidants by Neutrophils
53 BALF From CF and Non-CF Infants
54 Airway Inflammation in CF: Neutrophil-Dominated
55
56 Neutrophil-Mediated Inflammation in CF Lung Disease
57 Impairment of Complement-Mediated Phagocytic Host Defenses in CF
58 Other Harmful Effects of Neutrophil Elastase
59 Epithelial- Cell Cytokines and Inflammation in CF
60
61 CF Air Way Pro Inflammatory Mediators State Of Chronic Inflammation TNF-α,IL-1β,IL-6,IL-8,IL-17,IL-33.GM-CSF,G-CSF,HMGB-l TNF-α enhances neutrophil oxidative and secretory responses promotes cachexia associated with CF IL -1β- induces fever, stimulates acute phase responses promotes muscle protein catabolism TNF α and IL- 1β prime neutrophils, increasing their response to chemo attractants, surface expression of adhesion molecules CD11/CD18, ICAM-1 on endothelial cells GM-CSF delay neutrophil apoptosis and inhibit clearance of neutrophils from lung Pro inflammatory mediators integral component of inflammatory cascade
62 Complex Dysregulated Inflammatory Response In CF Involves multitude of stimuli, cells, signaling pathways transcription factors and products Most research in CF air way inflammation increased activation of inflammatory response Inability to terminate and resolve inflammation also plays a critical role CF air ways deficient in counter regulatory molecules IL-10, nitric oxide [NO].lipoxin-A2 [LXA2]
63 Anti Inflammatory Path Ways Inability To Terminate & Resolve Inflammation IL-10 terminates acute inflammatory response, down regulates production of pro inflammatory cytokines and chemokine's, inhibits pro inflammatory transcription factors induces neutrophil apoptosis T cell clones from CF patients compared to control produce less IL 10 after stimulation Decreased NO exacerbate abnormal ASL height, impair the ability of ASM to relax contribute to bronchial obstruction inhibit bacterial killing & promote inflammation Lipoxin-A4 lipid mediator promotes resolution of neutrophilic inflammation- reduced in stable CF pts. BAL fluid As important as pro inflammatory pathways
64
65
66
67 Bronchiectasis
68
69
70 Immune Hyperresponsiveness in CF Airways
71
72
73
74
75
76 Potential Drug Therapies for CF
77 CFF Drug Development Programs
78 Therapeutic Approaches to CF
79 Five-Year Actuarial Survival After Lung Transplantation as a Function of Diagnosis
80 Improving Antimicrobial Activity in the CF Airway Inhaled tobramycin- Tobi (Pathogenesis/Chiron) RSV Vaccine- (wyeth-lederle, P. Hiatt et al) Multicenter trial Potential for short and long term reduction in morbidity Dextran- (D. Speert et al)- Multiple actions including: interference with Pseudomonas attachment to epithelium. Xylitol- (J. Zabner et al) 5 carbon sugar, improves antimicrobial properties of airway surface liquid.
81 Improving Mucociliary Clearance in CF Airway Secretion Clearance Study (American Biosystems Inc. CFF) Comparison of Conventional Chest Physical Therapy, Flutter Device, and high Frequency Chest Wall Oscillation 22 centers Inhaled Hypertonic Saline Disrupts ionic bonds in airway secretions Multicenter trial in Australia (P. Bye et al) Purinergic Agonists- (Inspire Pharmaceuticals Inc.) Active alternative chloride channel Increase Ciliary activity Phase I trial (P. Noone et al)
82 Modulating Airway Inflammation in CF Dornase alfa- Pulmozyme (Genetech Inc.) Does early administration of rhdnase slow the decline in lung function? Multicenter, International Trial Elastase Inhibitors Recombinant alpha-one-antitrypsin (PPL Therapeutics plc) DMP 777- specific intracellular inhibitor rmnei- Monocyte/Neutrophil Elastase Inhibitor (CBRI)
83 Enzyme Therapy for CF Airways Secretions- Dornase Alfa: Overview
84 This history is off to a great start Gene therapy for CF will work Additional experiments in humans are needed Progress in other areas will impact on gene therapy for CF Dupont, Kosciusko Community, Lutheran, Rehabilitation, St. Joseph and The Orthopedic hospitals are owned in part by physicians.
85
86
87
88 Approaches to Gene Therapy of CF
89
90 Gene Therapy for CF Will Work but at the present, it does not work well enough
91
92
93
94
95 Towards Personalized CF Care: Genomics and Proteomics
96 Spanning the Globe Working Together
97 Cystic Fibrosis Encouraging Developments From The World Of Translational Medicine
98 Translational Medicine: Often described as an effort to carry scientific knowledge from bench to bedside, translational medicine builds on basic research advancesstudies of biological processes using cell cultures, for example, or animal models and uses them to develop new therapies or medical procedures.
99 Translational Medicine: Applied to Cystic Fibrosis: The development of new therapies directly related to the underlying mechanisms of disease that have been discovered in the laboratory
100 What Might Protein Repair Therapy for CF Look Like? Vocabulary 101: - CFTR corrector: Allows mutant CFTR to properly fold and locate to the cell membrane - CFTR potentiator: Improves CFTR function to allow chloride conductance
101 Reduced Quantity Reduced Function Normal CFTR quantity and function Little to no CFTR Some CFTR Gating Conductance Treatment approaches Class I Class II Correctors Class V Class III Class IV Potentiators MacDonald et al. Pediatr Drugs 2007;9:1-10; Zielenski. Respiration 2000;67:117-33; Welsh et al. Cystic fibrosis In: Valle et al, eds. OMMBID. McGraw-Hill Companies Inc;2004:part 21,chap 201; O Sullivan et al. Lancet 2009;373:
102 Mucociliary Clearance And Obstruction Periciliary Liquid (PCL) CFTR normal Surface Epithelial Cells Tenacious Mucus cytoplasmic CFTR CF
103 Lumacaftor Increases The Amount of F508del-CFTR at The Cell Surface Cultured F508del/F508del-human bronchial epithelial cells cilia CFTR nuclei untreated + lumacaftor Van Goor et al., PNAS 2011
104 Protein Repair Candidates Related to Genetic Classes of CFTR Mutations: Medications Recently Approved or In Clinical Trials: Ataluren: Class I mutations (W1282X) Orkambi: Class II mutations (F508del) Recently approved by FDA as Lumicaftor in combination with Ivacaftor (Kalydeco) in homozygous F508del CF patients Kalydeco: Class III mutations (G551D) FDA approved March 2012 and February 2014 for additional Class III mutations Kalydeco: Class IV mutations (R117H) FDA approved December 2014 Symdeko: Tezacaftor/Ivacaftor and Ivacaftor-2018 Class llmutations F508del homozygous and 26 other CFTR mutations sensitive in vitro to this combination
105 CFTR Potentiator for G511D Ivacaftor post approval observational studies 10 % improvement in FEV1 55 % reduction in exacerbations 2.7 Kg weight gain Pronounced CFTR functional improvement Restore 30 to 50 % of CFTR activity in HBE cells Mean sweat chloride of a change in 48.1 mmol/l Long term follow up persistent improvement in exacerbation frequency, rate of pulmonary decline by 50 % from -1.72% control -0.91% /year in treated group Improve mucus clearance and GI Ph, reduce pseudomonas isolation, causes bronchodilatation, reduce structural lung disease Improvement in bacterial load, host defense -potentially reverse structural lung damage turn back the clock
106 Symdeko For Delta F508 Homozygous Lung functions- 4.0 % improvement compared to placebo Pulmonary exacerbation 35 % reduction vs placebo BMI kg/m2 vs placebo not statistically significant CFQ-R respiratory domain 5.1 % increase vs placebo
107
108
109
110
111 References Vertex Pharmaceuticals Incorporated, de Jong PA, Et al. Eur Respir J. 2004; 23(1):93-97
Respiratory Pharmacology: Treatment of Cystic Fibrosis
Respiratory Pharmacology: Treatment of Cystic Fibrosis Dr. Tillie-Louise Hackett Department of Anesthesiology, Pharmacology and Therapeutics University of British Columbia Associate Head, Centre of Heart
More informationTransformational Treatments. PRESTON W. CAMPBELL, III, M.D. Executive Vice President for Medical Affairs
Transformational Treatments PRESTON W. CAMPBELL, III, M.D. Executive Vice President for Medical Affairs Symptom-based CF Therapies 45 Median Predicted Survival Age of US Patients with Cystic Fibrosis 41
More information"Management and Treatment of Patients with Cystic fibrosis (CF)
"Management and Treatment of Patients with Cystic fibrosis (CF) Dr. Malena Cohen-Cymberknoh Pediatric Pulmonology and CF Center Hadassah Hebrew-University Medical Center Jerusalem, Israel Afula, March
More informationTHE ROLE OF CFTR MUTATIONS IN CAUSING CYSTIC FIBROSIS (CF)
THE ROLE OF CFTR MUTATIONS IN CAUSING CYSTIC FIBROSIS (CF) Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210. Vertex and the Vertex triangle logo are registered trademarks for Vertex
More informationCystic Fibrosis Foundation Patient Registry 2013
5/9/2015 Targeting CFTR to Treat Cystic Fibrosis: Small Molecule Therapy Mary Ellen Kleinhenz, MD Director, UCSF Adult Cystic Fibrosis Program Professor of Medicine UCSF Division of Pulmonary, Critical
More informationMedical Policy An independent licensee of the Blue Cross Blue Shield Association
Cystic Fibrosis Transmembrane Page 1 of 13 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Prime Therapeutics
More informationMedical Policy An independent licensee of the Blue Cross Blue Shield Association
Cystic Fibrosis Transmembrane Page 1 of 11 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Prime Therapeutics
More informationPediatrics Grand Rounds 18 Sept University of Texas Health Science Center. + Disclosure. + Learning Objectives.
Disclosure Dr Donna Willey Courand receives research support from Cystic Fibrosis Therapeutics The Cystic Fibrosis Foundation Children with Special Health Care Needs Cystic Fibrosis 05: Improving Survival
More informationCYSTIC FIBROSIS OBJECTIVES NO CONFLICT OF INTEREST TO DISCLOSE
CYSTIC FIBROSIS Madhu Pendurthi MD MPH Staff Physician, Mercy Hospital Springfield, MO NO CONFLICT OF INTEREST TO DISCLOSE OBJECTIVES Epidemiology of Cystic Fibrosis (CF) Genetic basis and pathophysiology
More informationCystic Fibrosis the future
Cystic Fibrosis the future Pathophysiologic cascade Abnormal Gene Abnormal CFTR Therapy Gene replacement Protein replacement Gene read through therapy Abnormal sodium chloride & water movement through
More informationWhat is Cystic Fibrosis? CYSTIC FIBROSIS. Genetics of CF
What is Cystic Fibrosis? CYSTIC FIBROSIS Lynne M. Quittell, M.D. Director, CF Center Columbia University Chronic, progressive and life limiting autosomal recessive genetic disease characterized by chronic
More informationEvaluation of Patients with Diffuse Bronchiectasis
Evaluation of Patients with Diffuse Bronchiectasis Dr. Patricia Eshaghian, MD Assistant Clinical Professor of Medicine Director, UCLA Adult Cystic Fibrosis Affiliate Program UCLA Division of Pulmonary
More informationA Genetic Approach to the Treatment of Cystic Fibrosis
A Genetic Approach to the Treatment of Cystic Fibrosis Peter Mueller, PhD Chief Scientific Officer and Executive Vice President Global Research and Development Vertex Pharmaceuticals, Incorporated March
More informationDisclosures. Advances in the Management of Cystic Fibrosis: A Closer Look at the Roles of CFTR Modulation Therapy 10/28/2016
Advances in the Management of Cystic Fibrosis: A Closer Look at the Roles of CFTR Modulation Therapy Susanna A McColley, MD Associate Chief Research Officer Stanley Manne Children s Research Institute
More informationCystic Fibrosis: Progress in Treatment Management. Patrick A. Flume, M.D. Medical University of South Carolina
Cystic Fibrosis: Progress in Treatment Management Patrick A. Flume, M.D. Medical University of South Carolina Disclosures Grant support Mpex Pharmaceuticals, Inc Gilead Sciences, Inc Bayer Healthcare AG
More informationEnabling CF Therapeutic Development
Enabling CF Therapeutic Development PRESTON W. CAMPBELL, III, M.D. Executive Vice President for Medical Affairs No Disclosures Cystic Fibrosis In 1955 In 1955 most children with CF did not live long enough
More informationCystic fibrosis: hitting the target
Cystic fibrosis: hitting the target Heartland Collaborative Annual Meeting Friday, October 5, 2012 Thomas Ferkol MD 1938 1953 Cystic fibrosis: a historical timeline Cystic fibrosis (CF) of the pancreas
More informationPULMONARY SURFACTANT, ALPHA 1 ANTITRYPSIN INHIBITOR DEFICIENCY, AND CYSTIC FIBROSIS DR. NABIL BASHIR BIOCHEMISTRY/RESPIRATORY SYSTEM
PULMONARY SURFACTANT, ALPHA 1 ANTITRYPSIN INHIBITOR DEFICIENCY, AND CYSTIC FIBROSIS DR. NABIL BASHIR BIOCHEMISTRY/RESPIRATORY SYSTEM Pulmonary surfactant Pulmonary surfactant is (phospholipoprotein) complex
More informationOral Cystic Fibrosis Modulators
Oral Cystic Fibrosis Modulators Goals: To ensure appropriate drug use and limit to patient populations in which they have demonstrated to be effective and safe. To monitor for clinical response for appropriate
More informationA Quick Guide to the. I507del. Mutation CFTR SCIENCE
A Quick Guide to the I507del Mutation CFTR SCIENCE 2016 Vertex Pharmaceuticals Incorporated VXR-HQ-02-00045a(1) 03/2016 Loss of CFTR activity is the underlying cause of cystic fibrosis (CF) 1 Spectrum
More informationTHE ROLE OF CFTR MUTATIONS IN CAUSING CYSTIC FIBROSIS (CF)
THE ROLE OF CFTR MUTATIONS IN CAUSING CYSTIC FIBROSIS (CF) Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210. Vertex and the Vertex triangle logo are registered trademarks of Vertex
More informationCystic Fibrosis. Jennifer McDaniel, BS, RRT-NPS
Cystic Fibrosis Jennifer McDaniel, BS, RRT-NPS Overview Cystic fibrosis is the most common fatal, inherited disease in the U. S. CF results from a defective autosomal recessive gene One copy of gene =
More informationGoals Basic defect Pathophysiology Clinical i l signs and symptoms Therapy
CYSTIC FIBROSIS Lynne M. Quittell, M.D. Director, CF Center Columbia University Goals Basic defect Pathophysiology Clinical i l signs and symptoms Therapy What is Cystic Fibrosis? Chronic, progressive
More informationTargeted therapies to improve CFTR function in cystic fibrosis
Brodlie et al. Genome Medicine (2015) 7:101 DOI 10.1186/s13073-015-0223-6 REVIEW Targeted therapies to improve CFTR function in cystic fibrosis Malcolm Brodlie 1*, Iram J. Haq 2, Katie Roberts 2 and J.
More informationBriefing Document. FDA Pulmonary - Allergy Drugs Advisory Committee
FDA Advisory Committee Briefing Materials Page 1 of 157 Briefing Document FDA Pulmonary - Allergy Drugs Advisory Committee Ivacaftor for the Treatment of Cystic Fibrosis in Patients Age 6 Years and Older
More informationPharmacogenomics in Rare Diseases: Development Strategy for Ivacaftor as a Therapy for Cystic Fibrosis
Pharmacogenomics in Rare Diseases: Development Strategy for Ivacaftor as a Therapy for Cystic Fibrosis Federico Goodsaid Vice President Strategic Regulatory Intelligence Vertex Pharmaceuticals Is there
More informationA review of Cystic Fibrosis
A review of Cystic Fibrosis Jennifer Landry md F.R.C.P.(C) Pulmonary & Critical Care Medicine McGill University Health Center Cystic Fibrosis One of the most common lethal inherited AR disorders in the
More informationCase Study What is the Relationship Between the Cell Membrane and Cystic Fibrosis?
Names: Date: Case Study What is the Relationship Between the Cell Membrane and Cystic Fibrosis? Dr. Weyland examined a six month old infant that had been admitted to University Hospital earlier in the
More informationThe Future of CF Therapy
The Future of CF Therapy Peter J. Mogayzel, Jr., M.D., Ph.D. Eudowood Division of Pediatric Respiratory Sciences The Johns Hopkins School of Medicine Overview The Future of CF Therapy Personalized therapy
More informationA Case of Cystic Fibrosis
Name(s) Date A Case of Cystic Fibrosis Dr. Weyland examined a six month old infant that had been admitted to University Hospital earlier in the day. The baby's parents had brought young Zoey to the emergency
More informationNational Horizon Scanning Centre. Mannitol dry powder for inhalation (Bronchitol) for cystic fibrosis. April 2008
Mannitol dry powder for inhalation (Bronchitol) for cystic fibrosis April 2008 This technology summary is based on information available at the time of research and a limited literature search. It is not
More informationSymdeko. Symdeko (tezacaftor and ivacaftor) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.45.10 Subject: Symdeko Page: 1 of 5 Last Review Date: June 22, 2018 Symdeko Description Symdeko (tezacaftor
More informationThe role of Lipoxin A4 in Cystic Fibrosis Lung Disease
Volume No: 6, Issue: 7, March 2013, e201303018, http://dx.doi.org/10.5936/csbj.201303018 CSBJ The role of Lipoxin A4 in Cystic Fibrosis Lung Disease Valérie Urbach a,b,*, Gerard Higgins a, Paul Buchanan
More informationYou Can Observe a Lot By Just Watching. Wayne J. Morgan, MD, CM
You Can Observe a Lot By Just Watching Wayne J. Morgan, MD, CM Disclosures Genentech Epidemiological Study of Cystic Fibrosis, Scientific Advisory Group CF Foundation Data Safety Monitoring Board Registry/Comparative
More informationHOW DISEASE ALTERING THERAPY IS CHANGING THE GOALS OF TREATMENT IN CF
HOW DISEASE ALTERING THERAPY IS CHANGING THE GOALS OF TREATMENT IN CF Peter D. Sly MBBS, MD, FRACP, DSc OUTLINE Goals of CF treatment Drivers of early disease neutrophilic inflammation oxidative stress
More informationPA Update: Oral Cystic Fibrosis Modulators
Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119
More informationClinical Commissioning Policy Proposition: Dornase alfa inhaled therapy for primary ciliary dyskinesia (all ages)
Clinical Commissioning Policy Proposition: Dornase alfa inhaled therapy for primary ciliary dyskinesia (all ages) Reference: NHS England E03X05/01 Information Reader Box (IRB) to be inserted on inside
More informationKalydeco. Kalydeco (ivacaftor) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.45.03 Subject: Kalydeco Page: 1 of 6 Last Review Date: November 30, 2018 Kalydeco Description Kalydeco
More informationCystic Fibrosis. Presented by: Chris Belanger & Dylan Medd
Cystic Fibrosis Presented by: Chris Belanger & Dylan Medd Outline What is Cystic Fibrosis? Signs, Symptoms & Diagnosis Who does it effect? General effects on daily life Managing Cystic Fibrosis Exercise
More informationSupplementary appendix
Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Moss RB, Flume PA, Elborn JS, et al, on behalf
More informationDisclosures. Learning Objectives. What is Cystic Fibrosis? Background
39 th National Conference on Pediatric Health Care March 19-22, 2018 CHICAGO Disclosures The Vision and the Journey of Cystic Fibrosis: Newborn Screening to Breakthrough Therapy March 20, 2018 Cynthia
More informationOrkambi. Orkambi (lumacaftor/ivacaftor) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.45.06 Subject: Orkambi Page: 1 of 6 Last Review Date: November 30, 2018 Orkambi Description Orkambi (lumacaftor/ivacaftor)
More informationCF: Understanding the Biology Curing the Disease
CF: Understanding the Biology Curing the Disease Scott H. Donaldson, MD Associate Professor of Medicine Director, Adult CF Care Center University of North Carolina at Chapel Hill Defining the path Drilling
More informationWhat is the inheritance pattern (e.g., autosomal, sex-linked, dominant, recessive, etc.)?
Module I: Introduction to the disease Give a brief introduction to the disease, considering the following: the symptoms that define the syndrome, the range of phenotypes exhibited by individuals with the
More informationHLA and antigen presentation. Department of Immunology Charles University, 2nd Medical School University Hospital Motol
HLA and antigen presentation Department of Immunology Charles University, 2nd Medical School University Hospital Motol MHC in adaptive immunity Characteristics Specificity Innate For structures shared
More informationDrug Use Criteria: Ivacaftor (Kalydeco ) and Lumacaftor/Ivacaftor (Orkambi )
Texas Vendor Program Use Criteria: (Kalydeco ) and Lumacaftor/ (Orkambi ) Publication History Developed: October 2012 Revised: December 2017; February 2016; June 2014. Notes: Information on indications
More informationCYSTIC FIBROSIS Risk Factors Epidemiology Pathogenesis Defective protein synthesis (10%) Abnormal protein folding, processing & trafficking
CYSTIC FIBROSIS Risk Factors Caucasian Family history of CF Infection Exposure to allergens and tobacco Epidemiology Carrier frequency of 1 in 25 for Caucasians The most common lethal genetic disease affecting
More informationIVACAFTOR THE ISRAELI EXPERIENCE ADI DAGAN MD THE ISRAELI CF CENTER SHEBA MEDICAL CENTER, TEL-HASHOMER
IVACAFTOR THE ISRAELI EXPERIENCE ADI DAGAN MD THE ISRAELI CF CENTER SHEBA MEDICAL CENTER, TEL-HASHOMER February 21, 2014 U.S. Food and Drug Administration Approves KALYDECO (ivacaftor) for Use in Eight
More informationPediatrics Grand Rounds 13 November University of Texas Health Science Center at San Antonio. Learning Objectives
Nationwide Newborn Screening for Cystic Fibrosis: Finally Creating an Opportunity for All Patients to Have Better Outcomes Philip M Farrell, MD, PhD* University of Wisconsin-Madison *No disclosures other
More informationCystic Fibrosis Diagnosis and Treatment
Cystic Fibrosis Diagnosis and Treatment Financial Disclosures Personal financial relationships with commercial interests relevant to medicine, within the past 3 years: NJH site PI for AstraZeneca. As faculty
More informationAtypical cystic fibrosis: from the genetic causes to current and future treatments
Boston University OpenBU Theses & Dissertations http://open.bu.edu Boston University Theses & Dissertations 2016 Atypical cystic fibrosis: from the genetic causes to current and future treatments Quinn,
More informationClinical Commissioning Policy: Dornase alfa inhaled therapy for primary ciliary dyskinesia (all ages)
Clinical Commissioning Policy: Dornase alfa inhaled therapy for primary ciliary dyskinesia (all ages) Reference: NHS England: 16029/P NHS England INFORMATION READER BOX Directorate Medical Operations and
More informationCost-effectiveness of Ivacaftor (Kalydeco ) for the treatment of cystic fibrosis in patients age 6 years and older who have the G551D mutation
Cost-effectiveness of Ivacaftor (Kalydeco ) for the treatment of cystic fibrosis in patients age 6 years and older who have the G551D mutation January 2013 1. A rapid review submission on the drug ivacaftor
More informationBreathtaking science. Developing respiratory drugs to improve health and quality of life. H.C. Wainwright Global Life Sciences Conference April 2018
Breathtaking science Developing respiratory drugs to improve health and quality of life H.C. Wainwright Global Life Sciences Conference April 2018 www.veronapharma.com Forward-Looking Statements This presentation
More informationGENETIC TESTING: IN WHOM AND WHEN
GENETIC TESTING: IN WHOM AND WHEN Robert D Oates, M.D. Boston University School of Medicine My background in this field I was the first to link Cystic Fibrosis Mutations with Congenital Absence of the
More informationTay Sachs, Cystic Fibrosis, Sickle Cell Anemia and PKU. Tay Sachs Disease (also called Hexosaminidase deficiency)
Tay Sachs, Cystic Fibrosis, Sickle Cell Anemia and PKU Tay Sachs Disease (also called Hexosaminidase deficiency) Introduction 1. Tay Sachs is a rare condition named after 2 physicians, Tay and Sachs, who
More informationCystic Fibrosis Care at the University of Florida
Cystic Fibrosis Care at the University of Florida Objectives To introduce you to the University of Florida CF Center To review center specific data for the UF pediatric CF Center To review current status
More informationThe Cystic Fibrosis Gene. about. CF is one of the most common genetic diseases that cause death in both children and
Gill1 Peter Gill Malory Klocke Research Paper 02 August, 2011 The Cystic Fibrosis Gene Cystic fibrosis, better known as CF, is a genetic disease most people know very little about. CF is one of the most
More informationOpinion 7 November 2012
The legally binding text is the original French version TRANSPARENCY COMMITTEE Opinion 7 November 2012 KALYDECO 150 mg film-coated tablets B/56 (CIP code: 34009 266 060 5 3) Applicant: VERTEX INN ATC Code
More informationCystic Fibrosis as it relates to the neonate MARIANNE MUHLEBACH, MD PROFESSOR, DEPT. PEDIATRICS UNC CHAPEL HILL
Cystic Fibrosis as it relates to the neonate MARIANNE MUHLEBACH, MD PROFESSOR, DEPT. PEDIATRICS UNC CHAPEL HILL Objectives: At the end of the presentation the listeners will Be able to describe neonatal
More informationNACFC investor meeting. Dr Katja Conrath, Therapeutic Head CF Dr Piet Wigerinck, CSO NACFC November 2017 Copyright 2017 Galapagos NV
NACFC investor meeting Dr Katja Conrath, Therapeutic Head CF Dr Piet Wigerinck, CSO NACFC 2017 2 November 2017 Copyright 2017 Galapagos NV Disclaimer This presentation contains forward-looking statements,
More informationCYSTIC FIBROSIS (CF): THE CHALLENGE OF EARLY, SYSTEMIC PROGRESSION
CYSTIC FIBROSIS (CF): THE CHALLENGE OF EARLY, SYSTEMIC PROGRESSION A Program for the CF Center Care Team Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210. Vertex and the Vertex
More informationKey Points: References: Canadian data from the Canadian Cystic Fibrosis Registry 2015 Annual Report normal
1 2 3 Cystic fibrosis is a rare life-long genetic disease that affects approximately 4,000 people in Canada and about 70,000 worldwide regardless of race or ethnicity but is more common in Caucasians 1,2
More informationCystic Fibrosis. Cystic Fibrosis. Cystic Fibrosis 5/01/2011 CYSTIC FIBROSIS OF THE PANCREAS AND ITS RELATION TO CELIAC DISEASE. D ANDERSEN.
1938 OF THE PANCREAS AND ITS RELATION TO CELIAC DISEASE. D ANDERSEN. American Journal Diseases Children. : The beginning May 1938: 49 cases 25 20 15 Nos of cases 10 5 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 Age
More informationUNDERSTANDING THE EARLY, SYSTEMIC PROGRESSION OF CYSTIC FIBROSIS (CF) A Resource for the CF Center Care Team
UNDERSTANDING THE EARLY, SYSTEMIC PROGRESSION OF CYSTIC FIBROSIS (CF) A Resource for the CF Center Care Team Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210. Vertex and the Vertex
More informationSummary A pharmaceutical company which develops therapeutic products for
Innovative products for respiratory diseases Annual General Meeting October 2012 Pharmaxis - company overview Summary A pharmaceutical company which develops therapeutic products for human chronic respiratory
More informationAdvances in CF therapies and their effect on GI manifestations. Presenter Disclosure Daniel Gelfond, MD Relationship related to this presentation
Advances in CF therapies and their effect on GI manifestations Daniel Gelfond, MD University of Rochester WNY Pediatric Gastroenterology Presenter Disclosure Daniel Gelfond, MD Relationship related to
More informationFocus on Cystic Fibrosis. Cystic Fibrosis. Cystic Fibrosis
Focus on (Relates to Chapter 29, Nursing Management: Obstructive Pulmonary Diseases, in the textbook) Copyright 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Autosomal recessive, multisystem
More informationOverview of Cystic fibrosis in children. Apeksha Sathyaprasad, MD Pediatric pulmonologist
Overview of Cystic fibrosis in children Apeksha Sathyaprasad, MD Pediatric pulmonologist No conflicts of interest OBJECTIVES Review pathophysiology of pulmonary disease in cystic fibrosis Review diagnostic
More informationCaring for a person with cystic fibrosis
Caring for a person with cystic fibrosis Item Type Article Authors McDonagh, Yvonne;Meagher, Catherine Publisher Green Cross Publishing Journal Nursing in General Practice Download date 01/09/2018 03:18:31
More informationGenetic diseases. - chromosomal disorders (aneuploidy) - mitochondrial inherited diseases (female lineage transmission)
Genetic diseases - chromosomal disorders (aneuploidy) - monogenic diseases (mendelian transmission) - mitochondrial inherited diseases (female lineage transmission) HOWEVER: interaction gene-environment
More informationInflammation in cystic fibrosis: An update
Received: 24 April 2018 Accepted: 25 June 2018 DOI: 10.1002/ppul.24129 REVIEW Inflammation in cystic fibrosis: An update Erica A. Roesch MD 1 David P. Nichols MD 2 James F. Chmiel MD, MPH 1 1 Department
More informationA Place For Airway Clearance Therapy In Today s Healthcare Environment
A Place For Airway Clearance Therapy In Today s Healthcare Environment Michigan Society for Respiratory Care 2015 Fall Conference K. James Ehlen, MD October 6, 2015 Objectives Describe patients who will
More informationHuman Genetic Disorders
Human Genetic Disorders HOMOLOGOUS CHROMOSOMES Human somatic cells have 23 pairs of homologous chromosomes 23 are inherited from the mother and 23 from the father HOMOLOGOUS CHROMOSOMES Autosomes o Are
More informationCF: Information for Case Managers. Cindy Capen MSN, RN Pediatric Pulmonary Division University of Florida
CF: Information for Case Managers Cindy Capen MSN, RN capencl@peds.ufl.edu Pediatric Pulmonary Division University of Florida About your speaker 25+ years in pulmonary Coordinator for CF Center and CF
More informationDr Conroy Wong. Professor Richard Beasley. Dr Sarah Mooney. Professor Innes Asher
Professor Richard Beasley University of Otago Director Medical Research Institute of New Zealand Wellington Dr Sarah Mooney Physiotherapy Advanced Clinician Counties Manukau Health NZ Respiratory and Sleep
More informationHLA and antigen presentation. Department of Immunology Charles University, 2nd Medical School University Hospital Motol
HLA and antigen presentation Department of Immunology Charles University, 2nd Medical School University Hospital Motol MHC in adaptive immunity Characteristics Specificity Innate For structures shared
More informationTEST INFORMATION Test: CarrierMap GEN (Genotyping) Panel: CarrierMap Expanded Diseases Tested: 311 Genes Tested: 299 Mutations Tested: 2647
Ordering Practice Jane Smith John Smith Practice Code: 675 Miller MD 374 Broadway New York, NY 10000 Physician: Dr. Frank Miller Report Generated: 2016-02-03 DOB: 1973-02-19 Gender: Female Ethnicity: European
More informationLiver Disease in Cystic Fibrosis
Liver Disease in Cystic Fibrosis Basic Overview Clinical Aspects Management What Is Cystic Fibrosis? Autosomal recessive disease W-1:3000, H-1:10,000, AA-1:15,000 Mutations of CFTR defective Cl - transport
More informationBrand Name: Kalydeco. Generic: ivacaftor. Manufacturer 1 : Vertex Pharmaceuticals Incorporated
Brand Name: Kalydeco Generic: ivacaftor Manufacturer 1 : Vertex Pharmaceuticals Incorporated Drug Class 2,3 : Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Potentiator Uses: Labeled Uses 1,2,3,4,5
More informationCystic fibrosis: From the gene to the disease
Cystic fibrosis: From the gene to the disease Christiane Knoop, MD, PhD Institut de Mucoviscidose de l ULB Hôpital Erasme christiane.knoop@erasme.ulb.ac.be Cystic fibrosis «The infant that tastes of salt
More informationDiseases of the gastrointestinal system. H Awad Lecture 2: small intestine/ part 2 and appendix
Diseases of the gastrointestinal system H Awad Lecture 2: small intestine/ part 2 and appendix Malabsorption most important causes of malabsorption: Celiac disease tropical sprue Lactase deficiency Whipple
More informationCystic fibrosis: From childhood to adulthood. Eitan Kerem Department of Pediatrics and CF Center Hadassah University Hospital Jerusalem Israel
Cystic fibrosis: From childhood to adulthood Eitan Kerem Department of Pediatrics and CF Center Hadassah University Hospital Jerusalem Israel Vas deference H 2 O Cl - Na + H 2 O Na + Cl - Cl - Cl -
More informationOverview of the immune system
Overview of the immune system Immune system Innate (nonspecific) 1 st line of defense Adaptive (specific) 2 nd line of defense Cellular components Humoral components Cellular components Humoral components
More informationEfficacy of NaCl nebulized hypertonic solutions in cystic fibrosis
Acta Biomed 2014; Vol. 85, Supplement 4: 10-18 Mattioli 1885 Original article Efficacy of NaCl nebulized hypertonic solutions in cystic fibrosis Azienda Ospedaliero Universitaria Policlinico, DAI Scienze
More informationCystic fibrosis (CF) is the most frequent. Ivacaftor treatment in patients with cystic REVIEW. Isabelle Sermet-Gaudelus
Eur Respir Rev 2013; 22: 127, 66 71 DOI: 10.1183/09059180.00008512 CopyrightßERS 2013 REVIEW Ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation Isabelle Sermet-Gaudelus ABSTRACT:
More informationClinical Commissioning Policy: Ivacaftor for Cystic Fibrosis (named mutations)
Clinical Commissioning Policy: Ivacaftor for Cystic Fibrosis (named mutations) Reference: NHS England: A01/P/c NHS England INFORMATION READER BOX Directorate Medical Commissioning Operations Patients and
More information4.6 Small airways disease
4.6 Small airways disease Author: Jean-Marc Fellrath 1. INTRODUCTION Small airways are defined as any non alveolated and noncartilaginous airway that has an internal diameter of 2 mm. Several observations
More informationImmunology of Asthma. Kenneth J. Goodrum,Ph. Ph.D. Ohio University College of Osteopathic Medicine
Immunology of Asthma Kenneth J. Goodrum,Ph Ph.D. Ohio University College of Osteopathic Medicine Outline! Consensus characteristics! Allergens:role in asthma! Immune/inflammatory basis! Genetic basis!
More informationOpening Doors to CF Clinical Research: Change is Coming
Opening Doors to CF Clinical Research: Change is Coming Disclosures Contracts with sponsors for clinical trials conducted at UNC-Chapel Hill: CFFT NIH/NHLBI AbbVie Inc. Aptalis Pharma US, Inc. Janssen
More informationLesson Overview. Human Genetic Disorders. Lesson Overview Human Genetic Disorders
Lesson Overview 14.2 Human Genetic Disorders From Molecule to Phenotype There is a direct connection between molecule and trait, and between genotype and phenotype. In other words, there is a molecular
More informationRecently, the cystic fibrosis (CF) community celebrated the 25th
focused review A new era of personalized medicine for cystic fibrosis at last! Bradley S Quon MD MSc FRCPC 1,2, Pearce G Wilcox MD FRCPC 1,2 BS Quon, PG Wilcox. A new era of personalized medicine for cystic
More informationInnate Immunity. Bởi: OpenStaxCollege
Innate Immunity Bởi: OpenStaxCollege The vertebrate, including human, immune system is a complex multilayered system for defending against external and internal threats to the integrity of the body. The
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Donaldson SH, Bennett WD, Zeman KL, et al. Mucus clearance
More informationBronchiectasis. Examples include: Viral infections (measles, adenovirus, influenza)
Bronchiectasis What is Bronchiectasis? Bronchiectasis (pronounced bron-kee-ek'-tas-is) is a condition of the airways in the lungs. These airways (bronchial tubes) are tubelike structures that branch from
More informationMolecular Basis of Personalized Therapies for CF: Can We Treat All Patients?
CF Europe Meeting Molecular Basis of Personalized Therapies for CF: Can We Treat All Patients? Margarida D Amaral Brussels, 13 June 2015 The CF Pathogenesis Cascade 2 Defective CF Genes Deficient CFTR
More informationTRANSPARENCY COMMITTEE
The legally binding text is the original French version TRANSPARENCY COMMITTEE Opinion 5 November 2014 KALYDECO 150 mg, film-coated tablet B/56 (CIP: 34009 266 060 5 3) Applicant: VERTEX INN ATC code Reason
More informationPhase 3 EVOLVE & EXPAND Studies of Tezacaftor/Ivacaftor Combination Show Statistically Significant Improvements in Lung Function and Other Measures
Phase 3 EVOLVE & EXPAND Studies of Tezacaftor/Ivacaftor Combination Show Statistically Significant Improvements in Lung Function and Other Measures in CF Patients March 29, 2017 Agenda Introduction Michael
More informationA Cure for All: Leaving No One Behind. Assuring Effective Therapies for All Patients with Cystic Fibrosis
A Cure for All: Leaving No One Behind Assuring Effective Therapies for All Patients with Cystic Fibrosis Topics for Today s Presentation Demographics of the CF patient population in the modulator era
More informationCystic Fibrosis. Parkland College. Monica Rahman Parkland College. Recommended Citation
Parkland College A with Honors Projects Honors Program 2013 Cystic Fibrosis Monica Rahman Parkland College Recommended Citation Rahman, Monica, "Cystic Fibrosis" (2013). A with Honors Projects. 98. http://spark.parkland.edu/ah/98
More information