Amyloid Transthyretin (ATTR) Amyloidosis AN OVERVIEW
|
|
- Darleen Randall
- 5 years ago
- Views:
Transcription
1 Amyloid Transthyretin (ATTR) Amyloidosis AN OVERVIEW
2 AMYLOID TRANSTHYRETIN (ATTR) AMYLOIDOSIS ATTR amyloidosis is a rare, progressive, and fatal disease that manifests clinically with motor and sensory neuropathy, autonomic neuropathy, gastrointestinal disturbances, and cardiomyopathy 1-3 There are 2 main types of ATTR amyloidosis Hereditary ATTR amyloidosis affects multiple organs and body systems (eg, heart, nervous system, gastrointestinal tract, and kidney) 1,2,4 Wild-type ATTR amyloidosis primarily affects the heart 1,2 PATHOPHYSIOLOGY ATTR amyloidosis is caused by the buildup of amyloid fibrils in organs and tissues in the body 4 The amyloidogenic precursor in ATTR amyloidosis is transthyretin (TTR), a transport protein synthesized primarily by the liver 2,5,6 Normally, TTR comprises 4 single-chain monomers (ie, tetramer) 5 TTR gene mutations are thought to induce changes that result in weaker interactions between monomer subunits 5,7 Weakened interactions render the normal tetrameric assembly prone to dissociation into monomers that misfold and have a greater propensity for aggregation Misfolded protein accumulates, forming fibrils that deposit in tissues and organs MECHANISM OF AMYLOID FIBRIL FORMATION 4,8,9 *Amyloid fibrils can be caused by a variety of toxic intermediates, including small oligomers and amorphous aggregates. Modified with permission from Bulawa et al.
3 GENETICS TTR is encoded by a single-copy gene; however, more than 120 mutations have been identified 10,11 Hereditary ATTR amyloidosis is typically associated with a single amino acid substitution caused by a point mutation in the TTR gene 2,10,12,13 For example, valine to methionine substitution at position 30 () Most TTR mutations are amyloidogenic and promote instability of TTR tetramers 2,11 V122I is the most common mutation worldwide associated with hereditary ATTR amyloidosis with cardiomyopathy 1,4 In the United States, V122I is the most common mutation and primarily occurs in African American individuals 4,15 3%-4% of African American individuals are V122I carriers compared with 0.44% of white individuals and 0% of Hispanic individuals 2 Although V122I is commonly associated with cardiomyopathy, many patients with V122I have polyneuropathy 1 Hereditary ATTR amyloidosis is transmitted in an autosomal dominant manner, with variable penetrance 1 GENOTYPE-PHENOTYPE CORRELATION Specific genotypes are associated with predominant polyneuropathy or cardiomyopathy features; however, most mutations affect multiple organs and there is considerable heterogeneity in disease manifestations 1 is the most common mutation worldwide associated with hereditary ATTR amyloidosis with polyneuropathy 1,4 The highest occurrence of is in northern Portugal (incidence, 1 in 538 individuals); however, this mutation is also common in other regions of world 1,2,4 Although is commonly associated with polyneuropathy, many patients with have cardiomyopathy 1 G47A A36P R34T S50R C10R F33L Early onset Neurologic Modified with permission from Rapezzi et al. F64L T49A E89Q Late onset W41L H88R S23N T60A L111M I68L V122I CARDIAC G47A R34T S50R C10R F33L Early onset NEUROLOGIC A36P F64L T49A E89Q Late onset W41L H88R S23N T60A L111M I68L V122I Cardiac CLINICAL PRESENTATION ATTR amyloidosis is characterized by substantial clinical heterogeneity Nonspecific symptoms and manifestations overlap with more common disorders, hindering recognition of amyloidosis Bilateral carpal tunnel syndrome (CTS) is a common presenting manifestation in patients with ATTR amyloidosis and can be diagnosed up to 10 years before confirmation of ATTR amyloidosis Patients often have a history of CTS release surgery 18 ; in a single report, 100% of patients with amyloidosis had bilateral CTS and 70% of patients had a history of CTS surgery 19 Spinal canal stenosis has been detected in patients with ATTR amyloidosis and is a common misdiagnosis in patients with hereditary ATTR amyloidosis 16,20 Modified with permission from Rapezzi et al. TTR amyloid deposits have been detected in as many as ~50% of surgical specimens from patients with lumbar spinal canal stenosis 21
4 CLINICAL MANIFESTATIONS a OCULAR MANIFESTATIONS 22 Dark floaters Glaucoma Abnormal blood vessels in eye Pupillary abnormalities LUMBAR SPINAL STENOSIS 18 GI MANIFESTATIONS 22 Nausea and vomiting Early satiety Diarrhea Severe constipation Diarrhea/constipation Unintentional weight loss BILATERAL CARPAL TUNNEL 18, 19, 22 SYNDROME PERIPHERAL SENSORY-MOTOR NEUROPATHY 22 Nerve damage beginning in the hands and feet that can progress to the central part of the body CARDIOVASCULAR MANIFESTATIONS Irregular heart beat Conduction blocks Congestive heart failure (including shortness of breath, generalized fatigue, peripheral edema) Ventricular wall thickening with preserved ejection fraction and absence of left ventricular dilation NEPHROPATHY 22 Protein in urine Renal failure AUTONOMIC NEUROPATHY 22 Orthostatic hypotension Recurrent urinary tract infections (due to urinary retention) Sexual dysfunction Sweating abnormalities DIAGNOSIS Diagnostic challenges Low index of clinical suspicion coupled with lack of disease awareness impedes early and accurate diagnosis. Additional impediments to timely diagnosis include substantial clinical heterogeneity, nonspecific symptoms, and overlap with other medical conditions Substantial delays between initial symptoms and diagnosis are common in patients with ATTR amyloidosis, and misdiagnosis is common 17,26 Patients visit multiple physicians, often 5 or more, across a broad range of clinical specialties before receiving a diagnosis 17,26 Clinical presentation of ATTR amyloidosis is often indistinguishable from acquired monoclonal immunoglobulin light chain amyloidosis 13 Diagnostic procedures Tissue biopsy is necessary for confirmation 2,7,27 Congo red staining of amyloid is the gold standard for diagnosis 2,7 Congo red staining of tissue with resultant green birefringence when viewed under polarized light is pathognomonic for amyloid 2,7 Amyloid typing can be achieved using a variety of techniques Laser microdissection followed by mass spectrometry is the gold standard for amyloid typing 7 Genetic testing is recommended for confirmation and detection of specific TTR gene mutations 2,7 A diagnostic algorithm proposed by Gillmore, et al. based on myocardial radiotracer uptake on bone scanning has been developed for use in patients with cardiac ATTR amyloidosis 28 In addition to diagnosis, 99m technetium-pyrophosphate ( 99m Tc-PYP) scanning can differentiate cardiac manifestations of ATTR amyloidosis from acquired monoclonal immunoglobulin light chain amyloidosis 29 Use of myocardial radiotracer uptake on bone scanning may also eliminate the need for biopsy in patients with cardiac ATTR amyloidosis CNS, central nervous system; GI, gastrointestinal. Modified with permission from Conceição et al. a CNS symptoms can occur with certain TTR mutations but are not a common manifestation.
5 BURDEN OF DISEASE ATTR amyloidosis is a devastating, progressive disease that results in a rapid decline in quality of life Symptoms of hereditary ATTR amyloidosis impact multiple aspects of daily life, and disease burden increases with illness progression Patients report difficulty with fine motor skills, bathroom/self-care, movement/mobility, activities of daily living, an inability to stand for hours, run, and work Resource use is high among patients with hereditary ATTR amyloidosis, and hospitalization rates range from 14% to 30%, with a 14% to 24% rate for emergency visits 32 Functional health and well-being are severely compromised in patients with ATTR amyloidosis 33 More than half (55%) the patients with hereditary ATTR amyloidosis report that their mental health/outlook on life is impacted by amyloidosis and they have anxiety (71%), stress (62%), and depression (43%) 31 CURRENT TREATMENT AND LIMITATIONS UNMET NEEDS DIAGNOSIS Increasing clinical suspicion and disease awareness are high unmet needs Increased efforts are needed to keep amyloidosis front of mind among clinicians PATIENT ACCESS TO COORDINATED CARE Access to and coordination of care between amyloidosis centers of excellence and academic specialists is greatly needed APPROVED THERAPIES TO TREAT ATTR AMYLOIDOSIS Safe and effective disease-modifying therapies are needed that optimize patient quality of life, which is severely compromised by the disease, and improve clinical outcomes Treatment options are limited for patients with ATTR amyloidosis In the United States, no therapies for ATTR amyloidosis are approved by the US Food and Drug Administration (FDA) In Europe, tafamidis is approved for use in adults with stage 1 (stage 1 on a scale from 1 [lowest disease burden] to 3 [greatest disease burden]) symptomatic polyneuropathy to delay peripheral neurologic impairment 34 Current treatments, used off label, have limited effectiveness and are only used in specific patient populations 2,4 There is an urgent unmet need for treatments specifically designed for ATTR amyloidosis RESOURCES Amyloidosis Support Group Amyloidosis Foundation Amyloidosis Research Consortium My Amyloidosis Pathfinder Discover treatment centers and clinical trials that match your amyloidosis
6 REFERENCES 1. Coelho T, et al. Curr Med Res Opin. 2013;29(1): Ando Y, et al. Orphanet J Rare Dis. 2013;8: Suhr O, et al. J Int Med. 1994;235(5): Hawkins PN, et al. Ann Med. 2015;47(8): Saraiva MJ. FEBS Lett. 2001;498: Liz MA, et al. IUBMB Life. 2010;62(6): Leung N, Nasr SH, Sethi S. Blood. 2012;120(16): Coelho T, et al. Neurology. 2012;79(8): Disease Background - Transthyretin Amyloidosis. Transthyretin Amyloidosis Outcomes Survey (THAOS). Accessed January 3, Rowczenio DM, et al. Hum Mutat. 2014;35(9):E Hou X, Aguilar MI, Small DH. FEBS J. 2007;274(7): Connors LH, et al. Amyloid. 2003;10(3): Lachmann HJ, et al. N Engl J Med. 2002;346(23): Rapezzi C, et al. Eur Heart J. 2013;34(7): Maurer MS, et al. J Am Coll Cardiol. 2016;68(2): Nakagawa M, et al. Amyloid. 2016;23(1): Lousada I, et al. Orphanet J Rare Dis. 2017;12(suppl 1): Donnelly JP, Hanna M. Cleve Clin J Med. 2017;84(12 suppl 3): Ikram A, et al. J Card Fail. 2017;23(8):S11-S12 (P021). 20. Cortese A, et al. J Neurol Neurosurg Psychiatry. 2017;88(5): Yanagisawa A, et al. Mod Pathol. 2015;28(2): Conceição I, et al. J Peripher Nerv Syst. 2016;21(1): Coelho T, et al. A physician s guide to transthyretin amyloidosis. Research Gate Amyloidosis Foundation, s_ Guide_to_Transthyretin_Amyloidosis_Authored_by. Accessed January 3, Gertz MA. Am J Manag Care. 2017;23(7 suppl):s Galat A, et al. Eur Heart J. 2016;37(47): Lousada I, et al. Presented at: the First European Congress on Hereditary ATTR Amyloidosis. November 2015; Paris, France. 27. Castano A, et al. J Nucl Cardiol. 2016;23(6): Gillmore JD, et al. Circulation. 2016;133: Bokhari S, et al. Circ Cardiovasc Imaging. 2013;6(2): Adams D, Amitay O, Coelho T. Orphanet J Rare Dis. 2015;10(suppl 1):P Amyloidosis Foundation. Understanding the patient voice in hereditary transthyretin-mediated amyloidosis (ATTR amyloidosis). isabell_attr.pdf. Accessed January 3, Stewart M, et al. Value Health. 2013;16:A Lane T, et al. Orphanet J Rare Dis. 2015;10 (suppl 1): Vyndaqel [summary of product characteristics]. Sandwich, Kent, UK: Pfizer Limited; July human/002294/wc pdf. Accessed January 3, Bulawa C, et al. PNAS. 2012:109(24) Cover image was created in PyMol using PDB ID 1DVQ obtained from the RCSB PDB ( V.B. Oza, P. Raman, J.W. Kelly, J.C. Sacchettini [2000] Rational design of potent human transthyretin amyloid disease inhibitors. Nat Struct Biol. 7: ).
7 2018 Akcea Therapeutics, Inc. All rights reserved. TTR /18
Education Brochure. Hereditary ATTR amyloidosis A closer look at an inherited condition
Education Brochure Hereditary ATTR amyloidosis A closer look at an inherited condition What is hereditary ATTR (hattr) amyloidosis? hattr amyloidosis is caused by a gene change (mutation) that affects
More informationHereditary ATTR amyloidosis Talking to your healthcare professional about a hereditary condition
Healthcare Professional Discussion Guide Hereditary ATTR amyloidosis Talking to your healthcare professional about a hereditary condition This guide will give you some tips and strategies to help you start
More informationNeuropathy. Nerves before and after TTR. Márcia Waddington Cruz. CEPARM HUCFF-UFRJ.
Neuropathy. Nerves before and after TTR. Márcia Waddington Cruz. CEPARM HUCFF-UFRJ. Amyloidosis Amyloid deposit. Precursor proteins. Fibrilar ptn. Lesion to tissues. Mechanism? 2 A TTR. SSA or Wild Type
More informationHereditary ATTR (hattr) Amyloidosis: Polyneuropathy An Overview. Identifying the link can lead to a crucial diagnosis
Hereditary ATTR (hattr) Amyloidosis: Polyneuropathy An Overview Identifying the link can lead to a crucial diagnosis Hereditary ATTR (hattr) Amyloidosis: Polyneuropathy Information about mechanism of disease,
More informationHereditary ATTR (hattr) Amyloidosis: Cardiomyopathy An Overview. Identifying the link can lead to a crucial diagnosis
Hereditary ATTR (hattr) Amyloidosis: Cardiomyopathy An Overview Identifying the link can lead to a crucial diagnosis Hereditary ATTR (hattr) Amyloidosis: Cardiomyopathy Information about mechanism of disease,
More informationSummary of plenary sessions on October 31, 2015
4 th ATTR/Familial Amyloidosis Support Meeting October 31 to November 1, 2015 Hilton Chicago O Hare Airport hotel Summary of plenary sessions on October 31, 2015 1 Contents Welcome... 3 Why are we here?
More informationSafety and Efficacy of Inotersen in Patients with Hereditary Transthyretin Amyloidosis with Polyneuropathy (NEURO-TTR) Annabel K.
Safety and Efficacy of Inotersen in Patients with Hereditary Transthyretin Amyloidosis with Polyneuropathy (NEURO-TTR) Annabel K. Wang, MD University of California, Irvine ANA 2017 October 17, 2017 San
More informationCorporate Medical Policy
Corporate Medical Policy File Name: Origination: Last CAP Review: Next CAP Review: Last Review: patisiran_onpattro 11/2018 n/a 5/2019 2/2019 Description of Procedure or Service is a double-stranded small
More informationDaniel Judge presenting on behalf of the AG10 Phase 2 study investigators
Safety, Tolerability and Transthyretin Stabilization by AG10: A Phase 2, Randomized, Double-blind, Placebo-controlled Clinical Trial in Patients with Transthyretin Amyloid Cardiomyopathy and NYHA Class
More informationIMAGING IN CARDIAC AMYLOIDOSIS ; TRENDS IN DIAGNOSIS AND GUIDING THERAPY
IMAGING IN CARDIAC AMYLOIDOSIS ; TRENDS IN DIAGNOSIS AND GUIDING THERAPY Mohamed Abo Mandour, MD. Al-Azhar University Cardiac amyloidosis is an under appreciated cause of HF The bottom line pathologic
More information: A Study Examining the Prevalence of Transthyretin Mutations in Subjects Suspected of Having Cardiac Amyloidosis
: A Study Examining the Prevalence of Transthyretin Mutations in Subjects Suspected of Having Cardiac Amyloidosis 02 November 2015 1 Background and Rationale Cardiac amyloidosis is caused by extracellular
More informationreversing familial amyloid polyneuropathy naturally the raw vegan plant based detoxification regeneration workbook for healing patients volume 2
DOWNLOAD OR READ : REVERSING FAMILIAL AMYLOID POLYNEUROPATHY NATURALLY THE RAW VEGAN PLANT BASED DETOXIFICATION REGENERATION WORKBOOK FOR HEALING PATIENTS VOLUME 2 PDF EBOOK EPUB MOBI Page 1 Page 2 healing
More informationSAFETY AND EFFICACY OF INOTERSEN IN PATIENTS WITH HEREDITARY TRANSTHYRETIN AMYLOIDOSIS POLYNEUROPATHY (hattr-pn) Teresa Coelho, MD
SAFETY AND EFFICACY OF INOTERSEN IN PATIENTS WITH HEREDITARY TRANSTHYRETIN AMYLOIDOSIS POLYNEUROPATHY (hattr-pn) Teresa Coelho, MD Centro Hospitalar do Porto Porto, Portugal Disclosures Hospital Santo
More informationFamily Tree. Family Health Tree Map your family s history of hereditary ATTR amyloidosis
Family Tree Family Health Tree Map your family s history of hereditary ATTR amyloidosis Chart your family s health history This chart can help you map your family s health history and determine who may
More informationDiagnosis of Amyloidosis. Maria M. Picken MD, PhD Loyola University Medical Center Chicago
Diagnosis of Amyloidosis Maria M. Picken MD, PhD Loyola University Medical Center Chicago mpicken@lumc.edu 1 Outline Diagnosis of amyloidosis Fat pad Other 2 Amyloidoses protein folding disorders protein
More informationTTR-FAP: Diagnosis and treatment Zürich June 19,2014. Ole B Suhr Umeå University and University Hospital Department of Medicine Umeå Sweden
TTR-FAP: Diagnosis and treatment Zürich June 19,2014 Ole B Suhr Umeå University and University Hospital Department of Medicine Umeå Sweden Diagnosis of ATTR amyloidosis Clinical symptoms of ATTR- amyloidosis
More informationStepwise Approach for the Diagnosis of Amyloid Heart Disease
Stepwise Approach for the Diagnosis of Amyloid Heart Disease Mat Maurer, MD Columbia University Medical Center Arnold and Arlene Goldstein Professor of Cardiology April 13, 2019 Disclosures I am under-funded
More informationCARDIAC AMYLOIDOSIS IMAGING ERIC MARTIN MD
CARDIAC AMYLOIDOSIS IMAGING ERIC MARTIN MD DISCLOSURES Bayer Dalcor Pharma UK LTD Harvard Clinical Research Institute Heartflow Inc. NIH Vascular Dynamics Employee-Iowa Heart Center/Mercy-Des Moines BACKGROUND
More informationUpdate in Nuclear Imaging of Amyloidosis and Sarcoidosis
Update in Nuclear Imaging of Amyloidosis and Sarcoidosis Balaji Tamarappoo MD, PhD, Cedars-Sinai Heart Institute and Biomedical Imaging Research Institute Cedars-Sinai Medical Center Los Angeles, CA, USA.
More informationProgress in the Treatment of Cardiac Amyloidosis
Progress in the Treatment of Cardiac Amyloidosis Jignesh Patel MD PhD FACC FRCP Director, Cardiac Amyloid Program Medical Director, Heart Transplant Program Clinical Professor Cedars-Sinai Heart Institute,
More informationESC 2018 Tafamidis Analyst Briefing. August 27, 2018
ESC 2018 Tafamidis Analyst Briefing August 27, 2018 1 Forward Looking Statements This presentation includes forward-looking statements about, among other things, a potential indication for Tafamidis for
More informationUpdate on Treatments for Systemic Amyloidosis
Update on Treatments for Systemic Amyloidosis Laura M. Dember, M.D. Renal, Electrolyte and Hypertension Division University of Pennsylvania ANZSN Update Course Darwin, Australia September 2, 2017 Disclosure
More informationAmyloidoses are a heterogeneous group of disorders
REPORT Hereditary ATTR Amyloidosis: Burden of Illness and Diagnostic Challenges Morie A. Gertz, MD, MACP Amyloidoses are a heterogeneous group of disorders with a variety of clinical presentations characterized
More informationC. Quarta, L. Obici, S. Longhi, S. Perlini, A. Milandri, F. Del Corso, F. Perfetto, F. Cappelli, G. Merlini, C. Rapezzi
Hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: disease profile and differential diagnosis with hypertrophic cardiomyopathy and senile systemic amyloidosis C. Quarta, L.
More informationSubject: Patisiran (Onpattro )
09-J3000-16 Original Effective Date: 12/15/18 Reviewed: 11/14/2018 Revised: 01/01/19 Subject: Patisiran (Onpattro ) THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF
More informationHeart Failure Syndromes related to Unusual Cardiomyopathies
Heart Failure Syndromes related to Unusual Cardiomyopathies Juan M. Aranda Jr., M.D. Professor of Medicine Medical Director of Heart Failure/ Transplant Program University of Florida College of Medicine
More informationVarun Goel 1, Nathalie H Gosselin 2, Claudia Jomphe 2, Husain Attarwala 1, Xiaoping (Amy) Zhang 1, JF Marier 2, Gabriel Robbie 1
Population Pharmacokinetic (PK) / Pharmacodynamic (PD) Model of Serum Transthyretin (TTR) Following Patisiran Administration in Healthy Volunteers and Patients with Hereditary TTR-Mediated (hattr) Amyloidosis
More informationPrimary Amyloidosis. Kihyun Kim Div. of Hematology/Oncology, Dept. of Medicine, Sungkyunkwan Univ. School of Medidine Samsung Medical Center
Primary Amyloidosis Kihyun Kim Div. of Hematology/Oncology, Dept. of Medicine, Sungkyunkwan Univ. School of Medidine Samsung Medical Center Systemic Amyloidosis A group of complex diseases caused by tissue
More informationLatent Class Analysis to Classify Patients with Transthyretin Amyloidosis by Signs and Symptoms
Neurol Ther (2015) 4:11 24 DOI 10.1007/s40120-015-0028-y ORIGINAL RESEARCH Latent Class Analysis to Classify Patients with Transthyretin Amyloidosis by Signs and Symptoms Jose Alvir. Michelle Stewart.
More informationAmyloidosis: What to do and how to diagnose: An Update 2017
Amyloidosis: What to do and how to diagnose: An Update 2017 Jonathan L. Kaufman, MD Associate Professor Hematology & Oncology Winship Cancer Institute of Emory University Amyloidosis Protein Conformation/Deposition
More informationA Guide to Transthyretin Amyloidosis
A Guide to Transthyretin Amyloidosis Authored by Teresa Coelho, Bo-Goran Ericzon, Rodney Falk, Donna Grogan, Shu-ichi Ikeda, Mathew Maurer, Violaine Plante-Bordeneuve, Ole Suhr, Pedro Trigo 2016 Edition
More informationXiaoping (Amy) Zhang, Varun Goel, Husain Attarwala, and Gabriel Robbie. Alnylam Pharmaceuticals, Cambridge, USA
Patisiran Pharmacokinetics (PK), Pharmacodynamics (PD), and Exposure-Response (E-R) Relationship in Patients with Hereditary Transthyretin-Mediated (hattr) Amyloidosis Xiaoping (Amy) Zhang, Varun Goel,
More informationFrequencies and geographic distributions of genetic mutations in transthyretinand non-transthyretin-related familial amyloidosis
Clin Genet 2015: 88: 396 400 Printed in Singapore. All rights reserved Short Report Frequencies and geographic distributions of genetic mutations in transthyretinand non-transthyretin-related familial
More informationYES NO UNKNOWN. Stage I: Rule-Out Dashboard Secondary Findings in Adults ACTIONABILITY PENETRANCE SIGNIFICANCE/BURDEN OF DISEASE NEXT STEPS
Stage I: Rule-Out Dashboard GENE/GENE PANEL: TTR DISORDER: Hereditary transthyretin-related amyloidosis HGNC ID: 12405 OMIM ID: 105210 ACTIONABILITY PENETRANCE 1. Is there a qualifying resource, such as
More informationASSESSMENT OF CARDIAC AMYLOIDOSIS BY USING 18F-SODIUM FLUORIDE PET/MR IMAGING.
ASSESSMENT OF CARDIAC AMYLOIDOSIS BY USING 18F-SODIUM FLUORIDE PET/MR IMAGING. R. Abgral, M.Trivieri, M. Dweck, P. Robson, N. Karakatsanis, A. Lala, J. Contreras, R. Gopalan, P. Gorevic, V. Fuster, J.
More information6/6/2017. Uncommon Etiologies of Heart Failure: Cardiac Amyloidosis. Objectives. Case Presentation
Uncommon Etiologies of Heart Failure: Cardiac Amyloidosis Maria Fe White, MSN, FNP/ACNP-BC, FHFSA, CHFN Lead Nurse Practitioner Advance Heart Programs Comprehensive Transplant Center Objectives Describe
More informationAmyloidosis Information. A General Overview for Patients
Amyloidosis Information A General Overview for Patients www.amyloidosis.org Amyloidosis was first discovered 150 years ago by the well know German pathologist, Dr. Rudolf Virchow. Although the disease
More informationEidos Therapeutics, Inc.
Eidos Therapeutics, Inc. Precision medicine for transthyretin amyloidosis September 2018 update Eidos forward-looking statements This presentation contains forward-looking statements about Eidos Therapeutics,
More informationDiagnostic approach to cardiac amyloidosis: A case report
Diagnostic approach to cardiac amyloidosis: A case report Georgia Vogiatzi, MD, MSc, PhD 1 st Cardiology Department, Hippokration Hospital, Athens Medical School Disclosures I have no relevant relationships
More informationClinical Profile FOR. Indication. Important Safety Information
Clinical Profile FOR The first and only FDA-approved RNAi treatment for the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. 1 Indication ONPATTRO (patisiran) is indicated for
More informationConference Call to Discuss FDA Approval of ONPATTRO (patisiran)
Conference Call to Discuss FDA Approval of ONPATTRO (patisiran) August 10, 2018 1 Agenda Welcome Christine Lindenboom Vice President, Investor Relations & Corporate Communications Introduction John Maraganore,
More informationCardiac Amyloidosis: The Zebra is Losing its Stripes
Internal Medicine Grand Rounds University of Texas Southwestern Medical Center February 1 st, 2019 Cardiac Amyloidosis: The Zebra is Losing its Stripes Justin L. Grodin, MD, MPH, FACC, FHFSA Assistant
More informationAmyloidosis. Philip Hawkins National Amyloidosis Centre UCL & Royal Free Hospital, London
Amyloidosis Philip Hawkins National Amyloidosis Centre UCL & Royal Free Hospital, London Amyloid Abnormal extracellular fibrillar protein deposit in tissues Pathognomonic red-green birefringence after
More informationTechnetium-99m Pyrophosphate Scintigraphic Finding in Cardiac Amyloidosis: A Case Report
Technetium- Pyrophosphate Scintigraphic Finding in Cardiac Amyloidosis: A Case Report Pei-Ying Hsu 1,2, Yen-Wen Wu 2,3, Lung-Chun Lin 3, Su-Rong Hung 2, Kai-Yuan Tzen 2, Ruoh-Fang Yen 2 1 Division of Nuclear
More informationManagement of Heart Failure in Older Adults
Management of Heart Failure in Older Adults New Data, New Guidelines, New Challenges JOSE NATIVI, MD, MSCI Assistant Professor of Medicine Cardiovascular Director Amyloidosis Program DISCLOSURES - Advisory
More informationAmyloidosis- What does it have to do with Myeloma? Anita D Souza, MD, MS Froedtert & MCW Cancer Center Milwaukee, WI
Amyloidosis- What does it have to do with Myeloma? Anita D Souza, MD, MS Froedtert & MCW Cancer Center Milwaukee, WI Objectives Types of amyloidosis How does amyloidosis form? How is amyloidosis diagnosed?
More information04 July 2016 ISA Uppsala, Sweden
Phase 2 Open-Label Extension (OLE) Study of Revusiran An Investigational RNAi Therapeutic for the Treatment of Patients with Transthyretin Amyloidosis with Cardiomyopathy 04 July 2016 ISA Uppsala, Sweden
More informationActa Neurologica Belgica Single-centre experience on transthyretin familial amyloid polyneuropathy: case series and literature review
Acta Neurologica Belgica Single-centre experience on transthyretin familial amyloid polyneuropathy: case series and literature review --Manuscript Draft-- Manuscript Number: Full Title: Article Type: Corresponding
More informationNew approaches in amyloidosis. Philip Hawkins National Amyloidosis Centre UCL & Royal Free Hospital, London
New approaches in amyloidosis Philip Hawkins National Amyloidosis Centre UCL & Royal Free Hospital, London Systemic Amyloidosis Fatal protein misfolding/aggregation disease caused by accumulation of fibrillar
More informationA faint in the emergency department (due to primary systemic amyloidosis
104 PRACTICAL NEUROLOGY NEUROLOGICAL RARITIES A faint in the emergency department (due to primary systemic amyloidosis Michele T. M. Hu*, Carolyn M. Gabriel*, Helen J. Lachmann, Rosalind King, Philip N.
More informationAmyloidosis and Waldenström s Macroglobulinemia
Amyloidosis and Waldenström s Macroglobulinemia Morie A. Gertz, Giampaolo Merlini, and Steven P. Treon Primary systemic amyloidosis is an immunoglobulin light chain disorder that is 1/5th as common as
More informationLate-onset Transthyretin (TTR)-familial Amyloid Polyneuropathy (FAP) with a Long Disease Duration from Non-endemic Areas in Japan
doi: 10.2169/internalmedicine.1457-18 http://internmed.jp CASE REPORT Late-onset Transthyretin (TTR)-familial Amyloid Polyneuropathy (FAP) with a Long Disease Duration from Non-endemic Areas in Japan Zenshi
More informationAmyloidosis. Maria M. Picken MD, PhD
Amyloidosis Goals: To explain how amyloid forms and what diseases are caused by it Objectives 1. Explain why amyloid forms 2. When to suspect amyloidosis 3. How to diagnose amyloidosis 4. What are the
More informationDiagnosis and management of transthyretin familial amyloid polyneuropathy in Japan: red-flag symptom clusters and treatment algorithm
Sekijima et al. Orphanet Journal of Rare Diseases (2018) 13:6 DOI 10.1186/s13023-017-0726-x REVIEW Diagnosis and management of transthyretin familial amyloid polyneuropathy in Japan: red-flag symptom clusters
More informationGuideline of transthyretin-related hereditary amyloidosis for clinicians
Ando et al. Orphanet Journal of Rare Diseases 2013, 8:31 REVIEW Guideline of transthyretin-related hereditary amyloidosis for clinicians Open Access Yukio Ando 1,13*, Teresa Coelho 2, John L Berk 3, Márcia
More informationThe landscape of ATTR amyloidosis treatment
The landscape of ATTR amyloidosis treatment Teresa Coelho, M.D. Andrade s Center and Neurophysiology Department Hospital Santo António, Centro Hospitalar do Porto Portugal Disclosures Hospital Santo António
More informationHeart disease. Other symptoms too? FABRY DISEASE IN PATIENTS WITH UNEXPLAINED HEART CONDITIONS
Heart disease Other symptoms too? FABRY DISEASE IN PATIENTS WITH UNEXPLAINED HEART CONDITIONS You have been given this brochure because your heart condition may be linked to Fabry disease, which is a rare,
More informationCardiac amyloidosis an easy, but usually delayed diagnosis
M K pag 46 Mædica - a Journal of Clinical Medicine CASE REPORTS Cardiac amyloidosis an easy, but usually delayed diagnosis R. SILISTE, MD a ; I. CALANGEA, MD a ; F. VOINEA, MD a ; I. SAVULESCU-FIEDLER,
More informationReflecting on THAOS in 2016, and looking forward to 2017
Newsletter December 2016 Transthyretin Amyloidosis Outcomes Survey Scientific Board Meeting Summary Page 2 Spotlight Dr Arnt Kristen Page 3 THAOS today Page 4 Recent research from THAOS Page 5 ICON Project
More informationCryopyrin Associated Periodic Syndromes (CAPS) (CINCA/Muckle Wells/FCAS)
https://www.printo.it/pediatric-rheumatology/gb/intro Cryopyrin Associated Periodic Syndromes (CAPS) (CINCA/Muckle Wells/FCAS) Version of 2016 1. WHAT IS CAPS 1.1 What is it? Cryopyrin-Associated Periodic
More informationUnderstanding the Serum Free Light Chain Assays. Anne L Sherwood, PhD Director of Scientific Affairs The Binding Site, Inc.
Understanding the Serum Free Light Chain Assays Anne L Sherwood, PhD Director of Scientific Affairs The Binding Site, Inc. AL Amyloidosis: abnormality of proteins from Plasma Cells in the Bone Marrow Red
More informationSheena Surindran Grand Rounds 2/15/11
Sheena Surindran Grand Rounds 2/15/11 Affects 5 12 person per million / year 5 10% associated with myeloma Median survival without treatment is 12 40 months Most commonly affected organs are kidney, heart
More informationA celebration of 10 years of THAOS
Newsletter December 17 Transthyretin Amyloidosis Outcomes Survey Spotlight Fabio Barroso Page 2 A celebration of 10 years of THAOS This October saw the third THAOS Investigator meeting, along with the
More informationSelected age-associated changes in the cardiovascular system
Selected age-associated changes in the cardiovascular system Tamara Harris, M.D., M.S. Chief, Interdisciplinary Studies of Aging Acting Co-Chief, Laboratory of Epidemiology and Population Sciences Intramural
More informationSystemic amyloidosis with cardiac involvement
034 Cardiology Systemic amyloidosis with cardiac involvement Amyloidosis is a term used to describe a group of disorders consisting of abnormalities in and the accumulation of amyloid protein. This protein
More informationFAMILIAL AMYLOID POLYNEUROPATHY (TTR-FAP): Genetics and Treatment
FAMILIAL AMYLOID POLYNEUROPATHY (TTR-FAP): Genetics and Treatment Michelle Mezei BSc (Pharm), MDCM, FRCPC Neuromuscular Diseases Unit, VGH Division of Neurology, UBC 1 Learning Objectives To become familiar
More informationA Problem with Cardiac Amyloidosis. Defining Amyloidosis. Typical Amyloid Heart. Definition of a double-blind study:
A disease caused by the deposition of a proteinaceous material, derived from the misfolded breakdown products of a normal or abnormal protein. Typical Amyloid Heart Defining Amyloidosis TYPEOF AMYLOID
More informationORIGINAL ARTICLE. 123 I-MIBG scintigraphy reflects cardiomyopathy
ORIGINAL ARTICLE Imaging cardiac innervation in hereditary transthyretin (ATTRm) amyloidosis: A marker for neuropathy or cardiomyopathy in case of heart failure? Daphne L. Jonker, BSc, a Bouke P. C. Hazenberg,
More informationPeripheral Nerve Amyloidosis in Sural Nerve Biopsies. A Clinicopathologic Analysis of 13 Cases
Peripheral Nerve Amyloidosis in Sural Nerve Biopsies A Clinicopathologic Analysis of 13 Cases Bijal Rajani, MB, BS; Vakesh Rajani, MB, BS; Richard A. Prayson, MD Objective. Amyloidosis is a well-recognized
More informationAmyloidosis: Challenges in Diagnosis and Management
Amyloidosis: Challenges in Diagnosis and Management Ronald Witteles, MD Co-Director, Stanford Amyloid Center Associate Professor of Cardiovascular Medicine Program Director, Internal Medicine Residency
More informationWhole body amyloid deposition imaging by 123I-SAP scintigraphy van Rheenen, Ronald; Glaudemans, Andor; Hazenberg, Bouke
University of Groningen Whole body amyloid deposition imaging by 123I-SAP scintigraphy van Rheenen, Ronald; Glaudemans, Andor; Hazenberg, Bouke Published in: Tijdschrift voor Nucleaire Geneeskunde IMPORTANT
More informationAPOLLO Phase 3 Study of Patisiran Complete Results
Leo Living with hattr Amyloidosis APOLLO Phase 3 Study of Patisiran Complete Results November 2, 2017 Agenda Welcome Christine Lindenboom Vice President, Investor Relations & Corporate Communications Introduction
More informationMayo Clinic, Rochester, Minnesota; 2 Tufts Medical Center, Boston, Massachusetts; 3
NEOD001 Demonstrates Organ Biomarker Responses in Patients With Light Chain Amyloidosis and Persistent Organ Dysfunction: Final Results From a Phase 1/2 Study Morie A. Gertz, 1 Raymond L. Comenzo, 2 Heather
More informationFIBRILLARY GLOMERULONEPHRITIS DIAGNOSTIC CRITERIA, PITFALLS, AND DIFFERENTIAL DIAGNOSIS
FIBRILLARY GLOMERULONEPHRITIS DIAGNOSTIC CRITERIA, PITFALLS, AND DIFFERENTIAL DIAGNOSIS Guillermo A. Herrera MD Louisiana State University, Shreveport Fibrils in bundles 10-20 nm d Diabetic fibrillosis
More informationFamilial Amyloidosis. What Does it Mean for Your Family? Teresa Kruisselbrink, MS Certified Genetic Counselor Mayo Clinic, Rochester MN
Familial Amyloidosis What Does it Mean for Your Family? Teresa Kruisselbrink, MS Certified Genetic Counselor Mayo Clinic, Rochester MN The Journey Symptoms Meeting with Doctors Testing Diagnosis Treatment
More informationPathology of Complement Mediated Renal Disease
Pathology of Complement Mediated Renal Disease Mariam Priya Alexander, MD Associate Professor of Pathology GN Symposium Hong Kong Society of Nephrology July 8 th, 2017 2017 MFMER slide-1 The complement
More informationThe New England Journal of Medicine MISDIAGNOSIS OF HEREDITARY AMYLOIDOSIS AS AL (PRIMARY) AMYLOIDOSIS
MISDIAGNOSIS OF HEREDITARY AMYLOIDOSIS AS AL (PRIMARY) AMYLOIDOSIS HELEN J. LACHMANN, M.B., B.CHIR., DAVID R. BOOTH, PH.D., SUSANNE E. BOOTH, ALISON BYBEE, PH.D., JANET A. GILBERTSON, JULIAN D. GILLMORE,
More informationA classic case of amyloid cardiomyopathy
Images in... A classic case of amyloid cardiomyopathy Hayan Jouni, 1 William G Morice, 2 S Vincent Rajkumar, 3 Joerg Herrmann 4 1 Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
More informationCase 2 Dwayne A. Williams CASE 2
CASE 2 A 40- year- old male with no past medical history presents with bilateral flank pain and dark colored urine for 5 days. During family history taking, he states his father died from kidney failure
More informationTHAOS: Gastrointestinal manifestations of transthyretin amyloidosis - common complications of a rare disease
Wixner et al. Orphanet Journal of Rare Diseases 2014, 9:61 RESEARCH THAOS: Gastrointestinal manifestations of transthyretin amyloidosis - common complications of a rare disease Open Access Jonas Wixner
More informationDeclaration of conflict of interest. None to declare
Declaration of conflict of interest None to declare Risk management of coronary artery disease Arrhythmias and diabetes Hercules Mavrakis Cardiology Department Heraklion University Hospital Crete, Greece
More informationAmyloidosis and the Heart
Amyloidosis and the Heart Martha Grogan, MD October 26, 2013 2013 MFMER slide-1 Cardiac Amyloidosis Normal Heart Function How Amyloid affects the heart Symptoms Explanation of Heart Tests Treatment Options
More informationA Novel Variant Mutation of Transthyretin Ile73Val-Related Amyloidotic Polyneuropathy in Taiwanese
87 A Novel Variant Mutation of Transthyretin Ile73Val-Related Amyloidotic Polyneuropathy in Taiwanese Ming-Feng Liao, Hong-Shiu Chang Abstract- Purpose: Familial amyloidotic polyneuropathy (FAP) is an
More informationAmyloid Polyneuropathy and Myocardial Amyloidosis 10 Years after Domino Liver Transplantation from a Patient with a Transthyretin Ser50Arg Mutation
doi: 10.2169/internalmedicine.8434-16 Intern Med Advance Publication http://internmed.jp CASE REPORT Amyloid Polyneuropathy and Myocardial Amyloidosis 10 Years after Domino Liver Transplantation from a
More informationHereditary Fibrinogen Aα-Chain Amyloidosis
Patient Information Hereditary Fibrinogen Aα-Chain Amyloidosis Different types of amyloidosis Introduction AFib amyloidosis (fibrinogen Aα-chain amyloidosis) is a rare inherited genetic condition. People
More informationAL amyloidosis and autonomic neuropathy
AL amyloidosis and autonomic neuropathy This Infosheet explains what autonomic neuropathy is, what causes it in AL amyloidosis patients, what its symptoms are, how it is treated and some tips for self-management.
More informationOBSERVATION. Akira Yoshioka, MD; Yoko Yamaya, MD; Shinji Saiki, MD; Genjiro Hirose, MD; Kohei Shimazaki, MD; Masaaki Nakamura, MD; Yukio Ando, MD
OBSERVATION A Case of Familial Amyloid Polyneuropathy Homozygous for the Transthyretin Val30Met Gene With Motor-Dominant Sensorimotor Polyneuropathy and Unusual Sural Nerve Pathological Findings Akira
More informationThe Amyloidogenic V122I Transthyretin Variant in Elderly Black Americans
original article The Amyloidogenic V122I Transthyretin Variant in Elderly Black Americans C. Cristina Quarta, M.D., Joel N. Buxbaum, M.D., Amil M. Shah, M.D., M.P.H., Rodney H. Falk, M.D., Brian Claggett,
More informationNEOD001 for amyloid light-chain (AL) amyloidosis
NIHR Innovation Observatory Evidence Briefing: October 2017 NEOD001 for amyloid light-chain (AL) amyloidosis NIHRIO (HSRIC) ID: 10617 NICE ID: 8803 LAY SUMMARY Amyloid light-chain (AL) amyloidosis is caused
More informationProgram Highlights. Michael Pourfar, MD Co-Director, Center for Neuromodulation New York University Langone Medical Center New York, New York
Program Highlights David Swope, MD Associate Professor of Neurology Mount Sinai Health System New York, New York Michael Pourfar, MD Co-Director, Center for Neuromodulation New York University Langone
More informationProthena Corporation plc Overview
November 11, 2014 Prothena Corporation plc Overview 2014 Credit Suisse HC Conference The Arizona Biltmore Phoenix, AZ Forward-Looking Statements This presentation contains forward-looking statements. These
More informationCharacteristics of South Korean Patients with Hereditary Transthyretin Amyloidosis
JCN Open Access pissn 1738-6586 / eissn 2005-5013 / J Clin Neurol 2018;14(4):537-541 / https://doi.org/10.3988/jcn.2018.14.4.537 ORIGINAL ARTICLE Characteristics of South n Patients with Hereditary Transthyretin
More informationHereditary Cardiac Amyloidosis: A Case Report
Open Journal of Clinical & Medical Case Reports Hereditary Cardiac Amyloidosis: A Case Report Yu-hui Huang, MS*; Maya Viner, MD; Tushar Patel, MD; Radhika Sreedhar, MD, MS Volume 3 (2017) Issue 3 ISSN
More informationEDEMA IN A PATIENT WITH RECURRENT RESPIRATORY INFECTIONS - Case Report
EDEMA IN A PATIENT WITH RECURRENT RESPIRATORY INFECTIONS - Case Report Alain SOUPART, MD, PhD, FACP.hon Department of General Internal Medicine, Jolimont/Tubize and Erasmus University Hospital, Free University
More informationClinical history. 73 yo man with chest pain Systemic hypertension and WG Stress EKG N Stress echocardiogram: Cardiac catheterization: no CAD
CASE 8 Clinical history 73 yo man with chest pain Systemic hypertension and WG Stress EKG N Stress echocardiogram: Concentric hypertrophy Hypokinesis of LV-Inf Cardiac catheterization: no CAD Technique
More informationTNF Receptor Associated Periodic Syndrome (TRAPS)
https://www.printo.it/pediatric-rheumatology/gb/intro TNF Receptor Associated Periodic Syndrome (TRAPS) Version of 2016 1. WHAT IS TRAPS 1.1 What is it? TRAPS is an inflammatory disease characterised by
More information