rare neurological conditions in ireland: supporting ... · prof.anthony staines (dcu) dr. james...
TRANSCRIPT
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RARE NEUROLOGICAL CONDITIONS IN IRELAND:
SUPPORTING RESEARCH AND PRACTICE
Orla Hardiman BSc MD FRCPI MRIAProfessor of Neurology
Academic Director, Trinity Biomedical Sciences InstituteTrinity College Dublin
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Challenges for Service Development of Rare Disease
• Rare Diseases are heterogeneous
– Few clinical aspects in common other than the fact that they are rare
– Span all age ranges & all disciplines
– Differing needs
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Challenges for Service Development of Rare Disease
• Many conditions are under-reported-
– no population based database for most conditions
– Clinical initiatives driven by strong advocates
• some groups lose out
– No built in mechanism for sustainable care
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Consequences of Inadequate Services
• Knowledge deficit
– Delayed diagnosis
– Low quality of care
• Limited access to new drugs
• Poorer outcomes
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Solutions
• Population based databases
• Centralized services with “hub & spoke” model using existing resources
• Embedding research into clinical care
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Solutions
• Population based databases
• Centralized services with “hub & spoke” model using existing resources
• Embedding research into clinical care
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Population Based Datasets
• Inclusive
• Nobody is lost to follow up
• Allows accurate mapping of disease
• Improves outcomes
• Permit inclusion in clinical trials of novel agents
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Unique Advantages of Population Based Patient Registers
• Registers collect details of everybody in the country with a specific condition
• Most accurate reflection of range of disease types in a population
• Nobody is “lost to follow-up”
• Captures patients that might not attend specialist clinic
– Too old
– Too sick
– Too poor
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ALS/MND Register 2015
• Longest running ALS/MND Register in the world
– >2000 cases identified over 21 years
• 110 new cases every year
• 300 living with ALS/MND
• DNA bank containing >1000 samples from patients
and >1000 controls
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ALS risk map of Ireland at small area (SA) geometry
Rooney et al, Neurology, 2014
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PROGNOSTIC INDICATORS
Age of
onset
Cognitive &
behavioural
status
Site of onset
Rate of
progression
Genetic
background
Elamin et al., J Neurol 2015
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Solutions
• Population based databases
• Centralized services with “hub & spoke” model using existing resources
• Embedding research into clinical care
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Multidisciplinary Clinics Improve Use of Hospital Services & Reduce Length of Stay
• Lower number of hospital admissions
• 50% reduction in mean length of hospital stay
• 75% Planned (non-emergency) hospitalisations
Chio et al, JNNP, 2006
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Multidisciplinary Clinics are Good Value for Money
Van der Steen et al, ALS
Journal 2009
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MULTIDISCIPLINARY /SPECIALIST CLINICS IMPROVE OUTCOME
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PATIENT JOURNEY TO THE MDC
First Symptom to Attendance at a Multidisciplinary Clinic for Rare
Disease
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Galvin el al BMC Health Serv Res 2015
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Solutions
• Population based databases
• Centralized services with “hub & spoke” model using existing resources
• Embedding research into clinical care
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RESEARCH INTO RARE DISEASES…..
• Permits complete population based incidence & prevalence studies
• Identifies prognostic indicators
• Identifies subpopulation that can help to find new genes/ susceptibility factors
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RESEARCH INTO RARE DISEASES…..
• Informs health services
• Facilitates international collaborations
• Provides well characterized populations for clinical trials
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MANY RARE NEUROLOGICAL DISEASE HAVE A GENETIC BASIS
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POPULATION GENETICS
• Different populations may have different disease susceptibilities
• Finding genes help us understand biological pathways that cause /protect against diseases
• Finding and understanding pathways help develop new drugs
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IRISH ALS/MND GENOMICS
• 1000 GWAS from ALS/MND patients
• 700 GWAS from matched controls
• 750 Whole Genome Sequencing ALS/MND
• 350 Whole Genome Sequencing Controls
• Access to 16000 ALS And 7000 Control WGS
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GWAS CAN SEPARATE IRISH POPULATION FROM
ENGLISH
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MAPPING THE POPULATION STRUCTURE OF IRELAND USING GWAS
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INTERNATIONAL GWAS CONSORTIUM
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NOVEL DISCOVERIES USING IRISH ALS/MND GENOMICS DATA
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ALS AND SCHIZOPHRENIA SHARE COMMON SUSCEPTIBILITY GENES
McLaughlin et al, Unpublished
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MAPPING THE POPULATION STRUCTURE OF IRELAND USING GWAS
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RECONSTRUCTING FAMILIES:Identity-by-descent
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“SUPERFAMILIES”
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INTERNATIONAL GENE SEQUENCING PROJECT
• 13 countries, 22500 genomes!
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INTEGRATING RESEARCH THEMES
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PRECISION MEDICINE
Precision Medicine refers to the tailoring of medical treatment to the
individual characteristics of each patient…
..It relates to the ability to classify individuals into subpopulations
that differ in their susceptibility to a particular disease, in the
biology and/or prognosis of those diseases they may develop, or in
their response to a specific treatment.
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POPULATION BASED DISEASE REGISTER
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NEW DRUGS & BETTER TRIALS
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TeamClinicalBernie Corr
Ger Foley
Deirdre Murray
Lesley Doyle
Niamh Daly
Kitty McElligott
Imaging & EEGDr.Ed Lalor
Dr.Peter Bede
Dr.Bahman Nasseroleslami
Dr.Parames Iyer
Christina Schuster
Kieran Mohr
Michael Burke
Laboratory/NeuropharmDr. Julie Kelly
Dr. Alice Vajda
Gill Slator
NeuropsychologyDr.Niall Pender
Dr.Marwa Elamin
Tom Burke
Marta Pinto
Katy Lonnergan
EpidemiologyProf.Anthony Staines (DCU)
Dr. James Rooney
Mark Heverin (Register)
Caoife Madden
Genetics Prof Dan BradleyDr.Russell McLaughlinDr. Kevin Kenna
Academic NeurologyDominique Plant
Health ServicesProf.Anthony StainesProf.Charles Normand Dr. Miriam GalvinDr.Shelagh ConnollyDr.Katy TobinDr.Padraig RyanDr.Sinead Maguire Rebecca GaffneyIain MaysBrighid Gavin
EMG & BiomarkersDr.Ger Mullins
Dr.Taha Omar
Clinical TrialsLiz FogartyDr.Sam Bouazzaoui
Dr.Sinéad Maguire
Research ManagersDr.Alice VajdaMark Heverin
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International Collaborators
• European Network for the Cure of ALS– EMPOWER
– SOPHIA
– ALSCarE
– STRENGTH
• University of Utrecht
• Royal Victoria Hospital, Belfast
• Kings College London
• University of Edinburgh
• Massachusetts General Hospital
• University of Massachusetts
• Institute of Neurology, Havana
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RESEARCH FUNDING