APCDG-DMR - Universidade Nova de Lisboa

Transcripción

Vanessa Ferreira, PhD
President and Founder of the
Portuguese Association for CDG and other Rare Metabolic Diseases
(APCDG-DMR)
Member of the Spanish Association for CDG (AESCDG)
EUROGLYCANET CDG representative at European Platform for Rare Disease Registries (Epirare)
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OUTLINE
• INTRODUCTION ABOUT RARE DISEASES (RD)
 Rare diseases as a public health priority
• THE PATIENT’S VOICE
 APCDG-DMR: a non-profit organization
 Congenital Disorders of Glycosylation (CDG)
• ACTIVITIES DONE BY APCDG-DMR
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To support families (Information & Empowerment)
Networking
Awareness amongst public and health care professionals
Education
Scientific and clinical research
WHAT IS A RARE DISEASE?
A rare disease in Europe is a disease affecting less than 1 in
2,000 citizens
In the United States, a rare disease is any disease or condition
that affects 1 in 1,500 people
 29 million people affected in the EU
3 million people Spain
3 millions people in France (1 in 20)
600 000-800 000 people in Portugal
3.5 million people in the UK
1 million people in the Netherlands
25 million people USA
APCDG-DMR: Portuguese Association for CDG and other Rare Metabolic Diseases
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6,000 and 8,000 distinct rare diseases!
49 XXXXY 5p, Síndrome Acidemia Metilmalónica Homocistinuria, Tipo cbl C Acidemia Propiónica Acondroplasia Acondroplasia - Inmunodeficiencia Combinada Grave Adrenoleucodistrofia Agammaglobulinemia Ligada al Cromosoma X Aicardi
Goutières, Síndrome de Alagille, Síndrome de Albinismo Alexander, Enfermedad de Alfa 1 Antitripsina, Déficit de Alpers, Enfermedad de Alport, Síndrome de Amaurosis Retiniana Congénita de Leber Amiloidosis Primaria Familiar Andrade,
Enfermedad Anemia de Fanconi Angelman, Síndrome de Angioedema Hereditario Aniridia Apert, Síndrome de Arnold Chiari, Síndrome de Arteritis de Células Gigantes Artritis Crónica Juvenil Artritis Idiopática Juvenil Artritis Psoriásica Artrogriposis
Múltiple Congénita Artrogriposis, Síndrome de Aspartilglucosaminuria Ataxia de Friedreich Ataxia de Marie Ataxia Espinocerebelosa del Tipo 1 (SCA1) Ataxia Espinocerebelosa SK3 Ataxia Hereditarias Ataxia Olivopontocerebelosa Ataxia
Telangiectasia Atresia Aórtica Atresia Pulmonar con Comunicación Interventricular Atresia Pulmonar Septo Ventricular Intacto Atresia Tricúspide Atrofia Muscular Espinal Infantil Atrofia Muscular Espinal Proximal de Tipo 2 Atrofias Espinales Baller
Gerold, Síndrome de Batten Spielmeyer Vogt, Enfermedad de Beckwith Wiedemann, Síndrome de Behçet, Enfermedad de Berardinelli Seip, Síndrome de Blefaroespasmo B-Oxidación Mitocondrial Braquicefalia Aislada Budd Chiari, Síndrome de
Buerger, Enfermedad de C de Opitz, Síndrome Calambre del Escribano Calcinosis Canavan, Enfermedad de Cardiopatías Congénitas Carnitina, Síndromes por Déficit de Castleman, Enfermedad de Ceroido Lipofuscinosis Juvenil Ceroido
Lipofuscinosis Neuronal Charcot Marie Tooth, Enfermedad de Chediak Higashi, Enfermedad de Churg Strauss, Síndrome de Cistinosis Cistinuria Cistitis Intersticial Citocromo C Oxidasa, Déficit de Citomegalovirus, Síndrome del Citrulinemia
Coartación Aórtica Coffin Lowry, Síndrome de Coffin Siris, Síndrome de Colangitis Crónica Destructiva no Supurativa (CBP) Colangitis Primaria Esclerosante Coloboma del Iris Complejo Malformativo de Arnold Chiari Coproporfiria Hereditaria Corea
de Sydenham Cornelia de Lange, Síndrome de Coroidemia Craneosinostosis Primaria Crecimiento, Problemas de Crigler Najjar, Síndrome de Cromosoma X Frágil, Síndrome de Crouzon, Enfermedad de Dandy Walker, Síndrome de Danon,
Enfermedad de Defectos del Tabique Interauricular Defectos en la Biosíntesis de Testosterona Deficiencia Múltiple de Sulfatasas Déficit Congénito de HFE Déficit de 5a-reductora Deformidad de Sprengel Degeneración Macular Denys Drash,
Síndrome de Depleccóon del ADN Mitocóndrial, Síndrome Dilatación Aórtica Disferlina, Ausencia de Disfonía Espasmódica Disgenesia Gonodal XY Dismetrías Óseas Displasia Ectodérmica Displasia Ectodérmica Tipo Berlin Displásia Espondofisária
Displasia Ósea Displasia Ventricular Derecha Arritmógena (DVDA) Distonia Cervical Distonía Focal Distonía Multifocal Paroxística Distonía Neurodegenerativa Distonía Primaria Distonía que Responde a la Levodopa Distrofia Miotónica Distrofia
Muscular Congénita Tipo Fukuyama Distrofia Muscular de Cinturas Distrofia Muscular de Duchenne y de Becker Distrofia Muscular de Emery Dreyfuss Distrofia Muscular de Landouzy Dejerine Distrofia Muscular Infantil Distrofias Musculares Doble
Salida de Ventrículo Derecho Dolor Pélvico Crónico Duchenne Erb, Síndrome de Dumping, Síndrome de Ehlers Danlos, Síndrome de Ellis Van Creveld, Síndrome de Enanismo de Laron Epidermolisis Bullosa Epilepsia Mioclónica Progresiva
Escafocefalia Esclerodermia Esclerosis Lateral Amiotrófica Esclerosis Tuberosa Espina Bífida Estenosis Pulmonar Valvular Estenosis Subaórtica Fija Exostosis Múltiple Extrofia Cloacal Extrofia Vesical Fabry, Enfermedad de Factor IX, Déficit de
Fascitis Eosinofílica Fatiga Crónica, Síndrome de Felty, Síndrome de Fenilcetonúria o PKU Fibrodisplasia Osificante Progresiva Fibrosis Quística Fiebre Reumática Fucosidosis Galactosemia, Enfermedad de Gangliosidosis GM1 Gaucher
Schlagenhaufer, Enfermedad de Gilles de la Tourette, Síndrome de Glicosilación, Defectos Congénitos de la Glucogenosis Gorlin, Síndrome de Granulomatosa Cronica, Enfermedad Granulomatosis de Wegener Hemiplejia Alternante Infantil
Hemocromatosis Familiar Hemocromatosis Neonatal Hemofilia A Hemofilia C Hemoglobinopatía C - Forma Homocigota Hemoglobinopatía C Harlem Hemoglobinopatía D Hemoglobinopatía E Hemoglobinopatía Inestable Hemoglobinopatía J
Hemoglobinopatía M con Hemólosis Hemoglobinopatía S Hemoglobinuria Paroxística Nocturna Hepatitis Autoinmune, Formas Mixtas de Hermansky Pudlak, Síndrome de Hidrocefalia Hiper-IgM, Síndrome de Hiperlaxitud, Síndrome de
Hiperlisinemia Hiperostosis Frontal Interna Hipertensión Pulmonar Hipertensión Pulmonar Primaria o Idiopática Hipertensión Pulmonar Secundaria Hipocondroplasia Hipomagnesemia por Malabsorción Selectiva de Magnesio Hipopituitarismo
Hipoplasia de las Celulas de Leydig Hipotonía Muscular Congénita Histiocitosis Tipo II Histiocitosis X Hormona del Crecimiento, Déficit de Hunter, Síndrome de Huntington, Enfermedad de Huntington, Enfermedad de (Variante de Wesphal) Hurle
Scheie, Síndrome de Hurler, Enfermedad de I - Cell Ictiosis Vulgar Inmunodeficiencia Variable Común Insensibilidad a los Andrógenos, Síndrome de Insuficiencia Suprarrenal Primaria, Crónica, Adquirida Intolerancia Hereditaria a la Fructosa Isaacs,
Síndrome de Jacobsen, Síndrome de Job, Síndrome de Joseph, Enfermedad de Joubert, Síndrome de Kawasaki, Síndrome de Kearns Sayre, Síndrome de Kennedy, Enfermedad de Kleine Levin, Síndrome de Klinefelter, Síndrome de Klippel Feil,
Síndrome de Krabbe, Enfermedad de Leigh, Síndrome de Lesch Nyhan, Síndrome de Leucemia Linfocítica Crónica Leucodistrofia Leucodistrofia Metacromática Linfangioleiomiomatosis Lowe, Enfermedad de Lupus Discoide Eritematoso Lupus
Eritematoso Sistémico Malformaciones Craneocervicales Manosidosis Marfan, Síndrome de Maroteaux Lamy, Síndrome de Marshall Smith, Síndrome de Mastocitosis Maullido del Gato, Síndrome del McArdle, Enfermedad de McCune Albright,
Síndrome de McLeod, Síndrome de Melas, Síndrome de MERRF, Síndrome Miastenia Gravis Miller Dieker, Síndrome de Miocardiopatía Dilatada Idiopática Mitocondrial Mioneurogastrointestinal, Síndrome (MNGIE) Miopatía de Multicore Miopatía
Mitocondrial Miopatía Nemalínica Miopatías Congénitas Miopatías Metabólicas Mitoconfrial, Enfermedad Mixta del Tejido Conectivo, Enfermedad de Moebius, Síndrome de Morquio, Enfermedad de Mucolipidosis Tipo 2 Musculares,
Enfermedades Narcolepsia NARP, Síndrome de Natowicz, Síndrome de Nefronoptisis Neuramidasa, Deficiencia de Neurinoma del Acústico Neurofibromatosis Central Neurofibromatosis de Von Recklinghausen Neuromusculares, Enfermedades
Neuropatía Motora Multifocal Nevus Nevus Gigante Congénito Niemann Pick, Enfermedad de Nonne, Síndrome de Noonan, Síndrome de Núcleo Central, Enfermedad de Nutrición Parenteral Oculo Cerebro Renal, Síndrome de Oftalmoplegia
Externa Progresiva Osteogénesis Imperfecta Osteonecrosis Panhipopituitarismo Paraparesia Espástica Familiar Paraparesia Espástica Tropical Parry-Romberg, Síndrome de Pearson, Síndrome Pelizaeus Merzbacher, Enfermedad de Pénfigo Benigno
Crónico Familiar de Hailey-Hailey Pénfigo Foliáceo Pénfigo Vulgar Penfigoide Ampollar Pénfigoide Bulloso Penfigoide Cicatricial Penfigoide Gestacional Persona Rígida, Sindrome de la Peutz Jeghers, Síndrome de Pfeiffer, Síndrome Picnodisóstosis
Pierre Robin, Síndrome de Plagiocefalia Poems, Síndrome de Poland, Síndrome de Poliangeitis Microscópica Polineuropatía Amiloide Familiar (Tipo 1) Polineuropatía sensitivo-motora desmielinizante crónica Polineuropatías Poliquistosis Renal
Autosómica Dominante (PQRAD) Poliquistosis Renal Autosómica Recesiva Pompe, Enfermedad de Porfiria Aguda de Doss Porfiria Aguda Intermitente Porfiria Cutánea Tarda Porfiria Eritropoyética Congénita Porfiria Hepática Variegata Post Polio,
Síndrome de Prader Willi, Síndrome de Primarios Inmunitarios, Déficit de Prostatitis Crónica Proteus, Síndrome de Protoporfiria Eritropoyética Pseudo Hurler Polidistrofia Pseudoxantoma Elástico Púrpura de Schonlein Henoch Químico Múltiple,
Síndrome Quiste Aracnoideo Quiste de Tarlov Rapp Hodgkin, Síndrome de Raynaud, Enfermedad Reiter, Síndrome de Retinosis Pigmentaria Retinosquisis Rubinstein Taiby, Enfermedad de Russell Silver, Síndrome de Sandhoff, Enfermedad de
SanFilippo, Síndrome Santavuori, Enfermedad de Schwartz-Jampel, Síndrome de Sialidosis Síndrome de Rett Siringomielia Situs Inversus Cardiopatía Sjögren Primario, Síndrome de Sly, Síndrome de Smith Magenis, Síndrome de Sotos, Síndrome de
Stargardt, Enfermedad de Stickler, Síndrome de Still del Adulto, Enfermedad de Takayasu, Enfermedad de Talasemia Mayor Talasemia Minor Tay Sachs, Enfermedad de Telangiectasia Hemorrágica Hereditaria Tetralogía de Fallot Tirosinemia Tipo I
Transposición de Grandes Vasos Trisomia Cariotipo 47 XXX Turner, Síndrome de Usher, Síndrome de VACTERL Vasculitis Necrosante Generalizada Vasculitis Predominante Cutánea Ventrículo Único Von Gierke, Enfermedad de Von Hippel Lindau,
Síndrome de Von Willebrand, Enfermedad de WAGR, Síndrome de Walker Warburg, Síndrome de West, Síndrome de Williams, Síndrome de Wilson, Enfermedad de Wiskott Aldrich, Síndrome de Wolff Parkinson White, Síndrome de Wolfram,
Síndrome de X-Frágil, Síndrome Zellweger, Síndrome de
number of scientific publications about rare diseases continues to increase
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CHARACTERISTICS OF RARE DISEASES
 Chronic
 Progressive
 Degenerative
 Life-threatening
 Disabling
 Lack or loss of autonomy
 Difficult to manage
 Patients are few and
geographically spread
 Research is fragmented
 Resources are limited
 Experts are few
 Specialised care centres for each
disease cannot exist in every
country
 Relevant information is little
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RARE DISEASES ORIGINS
The cell
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Clinical manifestations
Causes
Populations they affect
Severity and age of onset
80% Genetic origins
Nucleus
DNA (Deoxyribonucleic acid)
http://www.freedigitalphotos.net/images/view_photog.php?photogid=2888
• Bacterial or viral infections
• Allergies
• Environmental causes
• Degenerative or
proliferative basis
Non-genetic origins
Suggestions that susceptibility
may be genetically determined
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OUTLINE
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RARE DISEASES (RD) AS A PUBLIC HEALTH PRIORITY
EU Regulations on:
Orphan Drugs (1999),
Paediatric Use of Medicines (2006),
Advanced Therapies (2007),
Commission Communication (2008),
Council Recommendation on Rare Diseases (2009),
EU Directive on Cross Border Health Care establishes rare diseases
as a public health priority in its Article 13 (Brussels, 21 February 2011).
http://ec.europa.eu/health/rare_diseases/policy/index_en.htm
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Orphan Medicinal Product Regulation:
development costs > expected return on investment
7,000-8000 rare medical conditions , less than 300 have therapies available to treat
them
What are the EU incentives ?
Market Exclusivity for 10 years after grant of EU marketing authorisation
Fee Reductions: reduction of centralised regulatory fees via a special fund from EU budgetary
authority
Centralised Procedure: direct access to EMA centralised procedure for marketing authorisation
EU-Funded Research grants from Community & Member State programmes
Protocol Assistance: free scientific advice to optimise development
 Application for Orphan Designation demonstrate orphan criteria have
been met:
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life-threatening or debilitating nature of condition
medical plausibility
prevalence < 5 in 10,000 or unlikely to generate sufficient return on investment
no satisfactory methods exist or medicinal product will be of significant benefit
Diagnostic tool can apply for orphan designation
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Annual Numbers of Orphan Designations and
Marketing Authorizations in the EU
Orphan
Designations
Number
of
Products
Marketing
Authorizations
2010
Year
Source: EU Commission, Jan 2011
Orphan medicinal products on the market
Source: Dr Jordi Llinares, EMA, 2011
OUTLINE
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Networking
Education
PORTUGAL
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EURORDIS: European Organisation for Rare Diseases
 Founded 1997
 461 members (45 countries)
 Represents more than 4000 RD
 Mission:Facilitate participation of patients in patient groups and to
federate these patient groups with the goal of achieving a more powerful
unified voice
EurordisCare1
EURORDIS IS PRESENT IN MANY EUROPEAN INSTITUTIONS AND
PLATFORMS
Committee for Orphan Medicinal Products at the EMEA (COMP)
EMEA/Committee for Proprietary Medicinal Products (CPMP)
Working Group with Patients’ Organisations
Rare Disease Task Force at Directorate General for Health and
Consumer Protection
EU Health Policy Forum at DG Health and Consumer Protection
EU High Level Groups on Health Services and Medical Care
EurordisCare2 and EurordisCare3
Different consortiums for patient organisations with a role in Healthcare issues
http://www.eu-patient.eu/
http://www.epposi.org/
http://www.patientsorganizations.org/
http://www.efgcp.be/
Examples of patient involvement in European
Medicines Agency (EMA):
 Membership of the EMA Management Board
 Membership of three scientific Committees:
 COMP (Committee for Orphan Medicinal Products)
 PDCO (Paediatric Committee)
 CAT (Committee for Advanced Therapies)
 PCWP (Patients’ and Consumers’ Working Party)
 Ad-Hoc participation in the activities of the Committee for
Proprietary Medicinal Products (CHMP)
 Review of Product Information (EPAR summary and package
leaflet)
 Membership of the Working Group on Clinical Trials in Third
Countries
 Patients act as observers in the Pharmacovigilance Working
Party (PhVWP)
PROFESSIONALIZED PATIENT:
•Conference Scholarship Opportunities directed to families and
patients representatives:
Genetic Diseases of Children: Advancing Research & Care
V Congreso Internacional de Medicamentos Huérfanos y
Enfermedades Raras
•6th DIA Patient Advocacy
Fellowship Program
•EURORDIS SUMMER SCHOOL for patient advocates
in clinical trials and drug development
INFORMED PATIENT:
Disease knowledge plus an expertise in
the therapeutic field
Data collection , Interpretation, Reports
•APIFARMA (Associação Portuguesa da
Indústria Farmacêutica) training: Formação
sobre Ensaios Clínicos
•L’École de l’ADN (Nîmes University, France)
Health Technical Assessment (HTA) Summer School at the London
School of Economics (LSE)
Should treatment A be reimbursed in a national healthcare
system?
For which patients should it be provided?
For how long should patients receive the treatment?
Understanding Health Technology
Assessment (HTA): A guide Health Equality Europe
OUTLINE
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Our organization in brief
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Founded in 2010
Non-Profit Organization
42 members (2 Honorary
members)
2 rare metabolic diseases
covered
6 volunteers in Portugal,
Spain, USA and Australia
EURORDIS
(European
Organisation
for
Rare
Diseases) member
Annual budget and funding
sources
Global voice to fight against
impact of rare metabolic
diseases
Rosália Ferreira,
Social and
Advocacy Affairs
Filipe Oliveira
Website
manager
Sandra Pinto,
Accessibility and
Advocacy Affairs
Andrea Berarducci,
CDG USA
Vanessa Ferreira
Scientific and
Management
Merell Liddle,
CDG Australia
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Clinical
Research
Basic
Research
Causes?
Clinical
Manifestations
Patient
Medical
doctor
Congenital disorder of
glycosylation type 1A
Rare Disease
BAD PROGNOSIS
Premature aging
Gene
Mutation
Genetic counseling
Prenatal diagnosis
.
?
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NO CURE
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Vision and mission
Basic
Research
Patient-centred research
To improve care
Clinical
Research
FAMILIES
Medical doctor
•To support families
•Scientific and clinical research
(Information,
& Empowerment)
•Development treatments and
Orphan Drugs
•Networking
•Awareness
•Education
•Advocacy RDs as Public Health
issue & policy development
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Associação Portuguesa CDG e outras
Doenças Metabólicas Raras (APCDG-DMR)
Formed by:
Board of directors;
Executive Board;
Finance Board.
Medical-Scientific
Panel:
Gene expression regulation
Stem-cells field
Cellular and neurobiology
Regulation of the translation
control
Development and growth
control
Neurodevelopment
Rare Metabolic Diseases
Mitochondrial diseases, Pyruvate Dehydrogenase Deficiency
(PDH), Krebs cycle disorders, GLUT1 deficiency, defects of
creatine and carnitine transport, glycogenosis , Galactosemia ,
Frutosemia, Inborn errors of amino acid metabolism
(Alkaptonuria, Aspartylglucosaminuria, Methylmalonic acidemia,
Maple syrup urine disease, Homocystinuria, Tyrosinemia,
Trimethylaminuria, Hartnup disease, Biotinidase deficiency,
Ornithine carbamoyltransferase deficiency, Carbamoyl-phosphate
synthase I deficiency disease, Citrullinemia, Hyperargininemia,
Hyperhomocysteinemia,
Hyperlysinemias,
Nonketotic
hyperglycinemia,
Propionic
acidemia,
Hyperprolinemia),
neurometabolic diseases, Peroxisomal diseases ( Zellweger
syndrome, rhizomelic chondrodysplasia punctata type 1, Infantile
Refsum disease, Pipecolic acidemia, Hyperoxaluria type 1, AcylCoA oxidase deficiency, D-bifunctional protein deficiency, X-linked
adrenoleukodystrophy,
Dihydroxyacetonephosphate
acyltransferase deficiency, Neonatal adrenoleukodystrophy,
Acatalasia, α-Methylacyl-CoA racemase deficiency, RCDP Type 2,
RCDP Type 3, Adult Refsum disease-1, Mulibrey nanism),
Congenital Disorders of Glycosylation (CDG)
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OUTLINE
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Networking
Education
Congenital Disorders of Glycosylation (CDG):
A booming disease of sugars
DNA
mRNA
nucleus
P
cytoplasm
Phosphorylation
Translation
Protein
formation
Protein
Post-translational Modifications
Ac Acetylation
Ub Ubiquitination
Glycosylation
P
Ac
Ub
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Functions:
Transport (Example:Transferrin)
Structural (Example: collagens)
Immunologic (Immunoglobulins, histocompatibility
Adapted from: Guia Metabólica
antigens)
Cell attachment-recognition site (Example:
Glycan
+
various proteins involved in cell-cell (sperm-oocyte for
example), Virus-cell,bacterium –cell, and hormone-cell
interactions)
Regulation of development
Protein
Hemostasis (and Thrombosis)
Glycoprotein
Hormones (Example: Human Chorionic Gonadotropin
(HCG), Thyroid-stimulating hormone (TSH)
Affect folding of certain proteins
(Calnexin, for example)
Interact with specific carbohydrates (Lectins, or
antibodies for example)
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Glycoprotein
Correctly formed
Glycans are missing: Type I
Glycoprotein
Uncorrectly formed Glycans are not correctly formed: Type II
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Diagnosis of rare diseases is an important area
of concern!
Several Specialists
Several medical exams
Underrecognized
Delays in diagnosis
Without diagnosis patients and families cannot access effective
 treatment, therapy , manage their condition and
 access to social services
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CDG DIAGNOSIS
Screening techniques:
• Transferrin isoelectric focusing (TF-IEF)
• Capillary zone electrophoresis (CZE)
• High pressure liquid chromatography (HPLC)
Techniques for further
investigation of CDGs:
• Measurement enzymatic deficiency or the genetic
mutations
• Lipid linked oligosacharides (LLO) (type I)
• Apolipoprotein (Apo) CIII (type II)
• Glycan analysis (type II): mass spectrometry (ES-MS) or
MALDI-TOF
Confirmation of CDG
diagnosis
1999-2009:
oCDG I a – I g, …:
oCDG II a – II c, …:
• enzymatic deficiency (few enzymes are measurable)
• or the genetic mutations: Exome Sequencing
2009: PMM2-CDG (CDG-Ia)
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CONGENITAL DISORDERS OF GLYCOSYLATION
Source: Dr Hudson Freeze laboratory webpage
Defects in protein N-glycosylation (n=16)
Defects in protein O-glycosylation (n=7)
Defects in lipid glycosylation (n=3)
Defects in multiple glycosylation pathways and other pathways (n=17)
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Abnormal
fat pads
(CDG Ia)
Skin
Coloboma
Strabismus
(CDGIa; -Ic)
Eyes
Bleeding
tendency
Inverted nipples (CDGIa)
Icthyosis
(CDG If)
APCDG-DMR
Retinitis
pigmentosa
Optical
atrophy
Congenital nephrotic
syndrome (CDGIa)
Coagulation
Renal
↓clotting factor XI
activity
UNEXPLAINED
SYNDROME !!!!
↑ FSH, LH and
prolactin
Laboratory
Cardiomyopathy (dylated
or hypertrophic, (CDGIa
and X)
Heart
Pericardial
effusion
Cycling vomiting
(CDGIb)
Neurology
Gastrointestinal
Chronic diarrhea
(CDG Ib)
Muscular
hypotonia
Hydrops
fetalis
Growth
retardation
Skeletal/Growth
Failure to thrive
(Adapted from T. Marquard, 2003 , Eur J Pediatr and Dr Luísa Diogo,Coimbra,Portugal)
Specific treatment
• Specific treatment is available for only one CDG,
namely PMI-CDG (CDG-Ib):
– simple daily oral mannose supplementation is an effective
treatment for patients with this potentially lethal disorder
• Some patients with SLC35C1-CDG or leukocyte adhesion
deficiency type II respond to simple supplementation of oral
fucose (alleviates clinical symptoms)
• In PIGM-CDG that causes histone hypoacetylation, butyrate
increases PIGM transcription and its supplementation was able to
control seizures in one reported patient
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Symptomatic treatments and
preventive measures
Clinical feature
Failure to thrive
Consider nasogastric tube or gastrostomy
tube feeding
Strabismus
Glasses, patching, or surgery
Stroke-like episodes
Low doses of aspirin
Oral motor dysfunction
Consider consultation with a
gastroenterologist/nutritionist
Osteopenia
Bisphosphonate therapy in severe forms
Pericardial effusion
Corticosteroids and salicylic acid, pericardial
drainage
Scoliosis/kyphosis
Surgical treatment in severe forms
True hypothyroidism
L-thyroxine supplementation
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OUTLINE
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Networking
Education
Support families through such vital services as:
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CDG International eNewsletter (3 languages): International
Access to scientific articles
Leaflets
Social network:

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CDG united, CDG Family network,
AESCDG,
Les p’tits CDG,
Sindrome CDG
o Skype (apcdgedmr)
o Guide to understanding CDG (SP, EN and PTG)
http://www.guiametabolica.org/sites/default/files/guia_practica_familias_CDG.pdf
Support families through such vital services as:
o I LUSO-HISPANIC CDG MEETING, 21 -22 October, 2011
o Webpage (3 languages): http://sindromecdg.orgfree.com
o Work in progress:
o Expand Information: Model of Informative medical record
o Interactive
o Funds
Informative medical record:
oSynonymous
oClassification: MIM code, Orpha number
oand code by OMS ICD10 (when it is applied)
oFeatures of the disease:
oDefinition
oCauses
oClinical spectrum
oTreatment and management
oNumber of population affected
oBibliography
oLaboratories of diagnosis
oReference Medical doctor
oPatients organisations
Visibility
60 000 readers
3700 readers
3700 readers
OUTLINE
o
o
o
o
o
Networking
Education
Networking: Patient representatives at International level
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
“Ethics on Rare Diseases Research” (28 October, 2009), Madrid, Spain.
22 nd DIA Annual EuroMeeting Tutorial: Orphan Drugs (8 March, 2010), Mónaco.
22 nd DIA Annual EuroMeeting (8-10 March), Mónaco.
4th Annual Clinical Forum (11-13 October), Lisbon, Spain.
Europlan Conference, Orphan Drugs Group (5-6 November), Burgos, Spain.
V International Conference on Orphan Drugs and Rare Diseases (17-19 February, 2011), Sevilha, Spain.
VIII Basic Course on Inherited Diseases of Metabolism (22-24 March), Coimbra, Portugal.
23 rd DIA Annual EuroMeeting Tutorial: Orphan Drugs in the EU; From designation to Marketing Authorisation (28 March), Geneva, Switzerland.
23 rd DIA Annual EuroMeeting (28-30 March), Geneva, Switzerland.
Eurordis Membership Meeting (12-14 May), Amsterdam, Netherlands.
“Eurordis Summer School for Patient Advocates in Clinical Trials and Drug Development” (12-16 June), Barcelona, Spain
Health Technology Assessment Programme at London School of Economics (8 - 10 June), London, Uk.
8th European Cytogenetics Conference (2-5 July), Porto, Portugal.
Glycosciences Conference (8-10 September), Lisboa, Portugal.
Inborn Errors of Metabolism and Neurodegeneration (3-5 November), Porto, Portugal.
European Medicines Agency: Patients and consumers training session on product information review (29 November), London, Uk.
EGAN/ROCHE strategy workshop:”Data sharing and therapy development: possibilities and pitfalls” (12-13 January, 2012), Basel, Switzerland.
European Conference on Rare Diseases and Orphan Products (23-25 May), Brussels,Belgium.
26th International Carbohydrate Symposium (ICS2012) (22nd to 27th, July), Madrid, Spain.
Networking: Patient representatives at National level
Inborn Errors of Metabolism and Neurodegeneration
(3-5 November,2011), Porto, Portugal.
VII Social Responsability week, 2012, Lisbon, Portugal
40
Networking: Oral and poster presentations
2011:








“What’s CDG?” Rare Disease Symposia (22 January), Zaragoza, Spain.
“The Congenital Disorders of Glycosylation (CDG) networking” (2 June), Faculty of Medical Sciences, Universidade Nova de Lisboa, Portugal.
Invited by Dr Paula Videira.
“Empowerment of Congenital Disorders of Glycosylation (CDG) patients’ voice” (31 May), Câmara Municipal do Seixal, GAMA department.
Invited by Cristina Fernandes (GAMA coordinator)
“Flourishing opportunities to Congenital Disorders of Glycosylation (CDG) patients voice”, (8 July) Seixal, Portugal. Invited by Sofia Loução
(Health Department at Câmara Municipal do Seixal).
“The Congenital Disorders of Glycosylation (CDG) non-profit organization” (8 July), “Medical Genetics Center Jacinto de Magalhães, National
Institut of Health Ricardo Jorge, Porto, Portugal. Invited by Dr Dulce Quelhas.
“The role of patients in research”. Round table. Glycosciences Conference (8-10 September), Lisboa, Portugal. Invited by Professor Dr Amelia
Rauter (Member of the Steering Committee and Executive for Glycochemistry of the ESF Research Network Euroglycoscience Forum and
Secretary of IUPAC Division III Subcommittee on Biomolecular Chemistry).
“Empowerment of Congenital Disorders of Glycosylation (CDG) patients’ voice”. Poster presented at Inborn Errors of Metabolism and
Neurodegeneration (3-5 November), Porto, Portugal.
“Empowerment of Congenital Disorders of Glycosylation (CDG) patients’ voice” (27-29 November), Book of abstracts, 22nd Joint
Glycobiology Meeting, Lille, France.
2012:




“Congenital Disorders of Glycosylation from a patient advocate point of view” (17 January). Invited by Lysogene, Paris, France.
“Congenital Disorders of Glycosylation (CDG)” (30 January), Apifarma, Lisbon, Portugal. Invited by Apifarma.
“Empowerment of Congenital Disorders of Glycosylation (CDG) patients’ voice” European Conference on Rare Diseases and Orphan
Products (23-25 May), Brussels, Belgium.
“Partnership amongst families, researchers and physicians to decipher CDG”: 26th International Carbohydrate Symposium (ICS2012) (22nd
to 27th, July), Madrid, Spain.
41
OUTLINE
o
o
o
o
o
Networking
Education
Awareness amongst public and health care professionals:
the Fairy-tale in then languages!
http://www.guiametabolica.org/
Awareness amongst public and health care
professionals
Paz Briones
Belén
PérezDueñas
Mercedes Serrano
Maria A
Vilaseca
professionals
professionals
Andrea Berarducci,
CDG USA
http://www.cafepress.com/CDG_Community
professionals
23 of July 2012
11.00-11.30:J. Jaeken (Belgium): Congenital Disorders of Glycosylation (CDG): a
booming disease family
11.30-12.00: V. Ferreira (Portugal): Partnership amongst families, researchers and
physicians to decipher Congenital Disorders of Glycosylation (CDG).
professionals
57 leaflets
Fairy-tales(5 in total)
Libraries
professionals
http://www.eurordis.org/content/living-cdg-two-stories-one-shared-hope
professionals
“CDG Kit” (EN, ES and FR)
CONGENITAL DISORDERS OF GLYCOSYLATION (CDG)
Name, CDG patient representative
Country
Collaborators: Andrea Berarducci, Bas Holten, Vanessa Ferreira
Skype name: cdgawareness
http://www.guiametabolica.org/sites/default/files/CDG_AWARENESS_AND_DISSEMINATION_ang.pdf
Rare Connect Online Community: http://www.rareconnect.org/en/community/cdg
OUTLINE
o
o
o
o
o
Networking
Education
Education
 Escola Secundária de Caldas
das Taipas (Guimarães)
 “Pôr os doentes em primeiro
lugar” (Patient First Project)
 Escola Superior de Saúde do
Instituto Politécnico da Guarda:
o To
characterize
the
oganizations in Portugal
non-profit
 Play Decide Game:
o A game that contributes to the
improvement and
enhancement of
understanding of different issues related
to Rare Diseases
http://www.playdecide.eu/
“PÔR OS DOENTES EM PRIMEIRO LUGAR”
Education
IGM- INSTITUTO DE GENÉTICA MÉDICA
DOUTOR JACINTO MAGALHÃES,Porto, Portugal
Education: To boost projects amongst universities
Meta-analysis and summaries in several languages
• Medicine, Biochemistry, Biology
(genetics), psychology
• Support therapies
• Graphic designing (fairy-tale as
video)
• Media (Journalism)
• Social care (Pharmaeconomy):
Economic burden
• Glycosciences eLearning course
OUTLINE
o
o
o
o
o
Networking
Education
To boost and incentive scientific and clinical research
•
Organisation of events to link researchers, clinicians and patients:
 Potentiating collaborations amongst research laboratories
(Javier Corral, University of Murcia , Spain)
•
Writing research projects
(Paula Videira Lab, Faculty of Medical Sciences - New University of Lisbon; Principal Investigator in CEDOC)
•
Visibility
 Scientific and Medical Conferences
 CDG International eNewsletter
•
Partnership with patient groups, researchers and medical doctors
 CDG Online Community
 Epirare
Partnership with patient groups, researchers and
medical doctors: CDG Online community
http://www.rareconnect.org/en/community/cdg
medical doctors: CDG Online community
CDG patients group role:
•Improved visibility for patient organization.
•Play a role in communicating to the
community.
•Blog entries/Updates written by patient
organization
•Information
•Research news
•Policy developments
•Events
•Play a role in governance of the community.
Recruiting Moderators & Volunteers
Family Referral Directory:
connecting families that are living in the same
region.
Many CDG experts participated (USA, France,
Argentina, Spain, Netherlands, Italy, Belgium
and Portugal)
medical doctors: Epirare
•
•
•
•
European Platform for Rare Disease
Registries
European network to boost research,
diagnosis and treatment
Natural history of the disease
- Epidemiological research
Clinical research (patient recruitment for
clinical trials)
- Disease surveillance
- Disease follow-up
- Treatment evaluation (efficacy)
- Treatment monitoring (safety)
- Mutation database
- Genotype-phenotype correlation
- Benchmarking for improvement of quality of
care and development of clinical care
•
•
Guidelines
Social planning
59
FAMILIES+RESEARCHERS+ PHYSICIANS: RESULT!
Eva Morava
Marisa Giròs
Lourdes
Belén Dueñas
Dirk Lefeber
Paula Videira
Hudson Freeze
Carla Asteggiano
Belén Pérez G
Claúdio
Dirk Lefeber
Célia Cerdá
Donna
Krasnewich
José Samuel
Maria Prol
Daisy Rymen
Rosália
Marta
Maria Vilaseca
Mercedes Serrano
Paz Briones
Jaak Jaeken
60
TOWARDS A HOPE BY SUPPORTING
RESEARCH
Support
Research
Calls
Fellowships
Patients as advisors:
research driven by patients
needs
61
PATIENTS’ PRIORITIES AND NEEDS
FOR RARE DISEASE RESEARCH
62
Thanks to:
The CDG Patient’s Voice
CDG-patients organizations or foundations
CDG active patient representatives nucleus:
Netherlands, UK, Ecuador, Brazil, Finland, Australia
“the little fighters foundation for a cure”
Thanks to:
The CDG Patient’s Voice
Links from different associations:
Portugal: http://sindromecdg.orgfree.com/
Spain: http://webs.ono.com/aescdg/SINDROME_CDG/Bienvenidos.html
France: http://www.lesptitscdg.org/
USA: http://www.cdgfamilynetwork.org/
Canada: http://www.thefog.ca/
http://thelittlefightersfoundation.com/
Germany: https://www.cdg-syndrom.de/
Denmark: http://www.cdgforeningen.dk/
Sweden: http://www.cdgs.se/
[email protected]
Thanks to:
Families and members
We are grateful to all Medical Doctors and Researchers that are changing the landscape
of this rare metabolic disease all around the world! Their efforts are contributing to improve
scientific and medical diagnosis, clinical manifestations and they are doing many efforts in
order to find a treatment to CDG patients.
In Spain:
Dr Belén P Dueñas
Dr Maria Vilaseca
Dr Mercedes Serrano
Dr Paz Briones
Dr Marisa Giròs
Dr Belén pérez
Dr Célia P Cerdá
Dr Rafael Artuch
In Portugal:
Dr Elisa Teles,
Dr Luísa Diogo,
Dr Laura Vilarinho,
Dr Dulce Quelhas,
Dr Paula Garcia,
Dr Sílvia Sequeira,
Dr Paula Videira,
Dr Esmeralda Martins
L F cartoon
We are particularly grateful to:
Professor Jaak Jaeken
THINK METABOLIC, THINK CDG!
INTERVIEW
The challenges that families face?
Facing a rare disease diagnosis: challenges
 Delays in order to obtain the precise and accurate diagnosis:
Misdiagnosis
Passing through all sort of medical tests and procedures before an
accurate diagnosis
Understanding the diagnosis
Feeling guilty
Lack and unavailability of scientific and medical information related
to CDG (Language barrier)
Scarcity of experienced physicians and medical centers specialized
Struggling to identify and access available resources
Health care and social support services are designed for patients
with common diseases
Adult: follow-up done by family medical doctor for 10 years
69
Facing a Host of Unique Challenges
Lack Specialised care
centres
Sibling reaction
Integration in Society,
accessibility
and symptomatic
treatment
Treatment
Educational
Roadmap, delay
diagnosis
Social integration
Isolated,
Lack of
information
Lack of economic
support
Adult phase
Professional integration,
genetic counseling and
future
Lack support therapies,
psychologic support
70
How this activity helps the
association?
S
P
E
C
I
F
I
C
Education
Support Families:
Inform, Communicate,
Train and Empowerment
Research
Awareness amongst
public, health,
education and care
professionals
PATIENT ADVOCACY
G
O
A
L
S
To advocate for better
quality of life for
patients and their
families;
NATIONAL
UE and INTERNATIONAL
To support the
development and
approval of legislation:
Patient
Added
Value:
a patientcentred
Healthcare
supporting the rights and
specific needs in terms of
social support, infrastructure
and health care;
72
Sources of photos:
• Slide 5: from the left to the right
– http://www.freedigitalphotos.net/images/view_photog.php?photogid=1
499
45
09
962
39
741
280
367

APCDG-DMR - Universidade Nova de Lisboa

Transcripción

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