RARE NEUROLOGICAL
CONDITIONS IN IRELAND:
SUPPORTING RESEARCH AND
PRACTICE
Orla Hardiman BSc MD FRCPI MRIA
Professor of Neurology
Academic Director, Trinity Biomedical Sciences Institute
Trinity College Dublin
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
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
Consequences of Inadequate
Services
• Knowledge deficit
– Delayed diagnosis
– Low quality of care
• Limited access to new drugs
• Poorer outcomes
Solutions
• Population based databases
• Centralized services with “hub & spoke”
model using existing resources
• Embedding research into clinical care
Solutions
• Population based databases
• Centralized services with “hub & spoke”
model using existing resources
• Embedding research into clinical care
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
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
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
ALS risk map of Ireland at small
area (SA) geometry
Rooney et al, Neurology, 2014
PROGNOSTIC INDICATORS
Age of
onset
Cognitive &
behavioural
status
Site of onset
Rate of
progression
Genetic
background
Elamin et al., J Neurol 2015
Solutions
• Population based databases
• Centralized services with “hub & spoke”
model using existing resources
• Embedding research into clinical care
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
Multidisciplinary Clinics are Good
Value for Money
Van der Steen et al, ALS
Journal 2009
MULTIDISCIPLINARY /SPECIALIST
CLINICS IMPROVE OUTCOME
PATIENT JOURNEY TO THE MDC
First Symptom to Attendance at a
Multidisciplinary Clinic for Rare
Disease
Galvin el al BMC Health Serv Res 2015
Solutions
• Population based databases
• Centralized services with “hub & spoke”
model using existing resources
• Embedding research into clinical care
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
RESEARCH INTO RARE DISEASES…..
• Informs health services
• Facilitates international collaborations
• Provides well characterized populations for
clinical trials
MANY RARE NEUROLOGICAL
DISEASE HAVE A GENETIC BASIS
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
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
GWAS CAN SEPARATE
IRISH POPULATION FROM
ENGLISH
MAPPING THE POPULATION STRUCTURE OF
IRELAND USING GWAS
INTERNATIONAL GWAS CONSORTIUM
NOVEL DISCOVERIES USING IRISH
ALS/MND GENOMICS DATA
ALS AND SCHIZOPHRENIA SHARE
COMMON SUSCEPTIBILITY GENES
McLaughlin et al, Unpublished
MAPPING THE POPULATION STRUCTURE OF
IRELAND USING GWAS
RECONSTRUCTING FAMILIES:
Identity-by-descent
“SUPERFAMILIES”
INTERNATIONAL GENE
SEQUENCING PROJECT
• 13 countries, 22500 genomes!
INTEGRATING RESEARCH
THEMES
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.
POPULATION BASED DISEASE REGISTER
NEW DRUGS & BETTER TRIALS
Team
Clinical
Neuropsychology
Bernie Corr
Ger Foley
Deirdre Murray
Lesley Doyle
Niamh Daly
Kitty McElligott
Dr.Niall Pender
Dr.Marwa Elamin
Tom Burke
Marta Pinto
Katy Lonnergan
Imaging & EEG
Epidemiology
Dr.Ed Lalor
Dr.Peter Bede
Dr.Bahman Nasseroleslami
Dr.Parames Iyer
Christina Schuster
Kieran Mohr
Michael Burke
Prof.Anthony Staines (DCU)
Dr. James Rooney
Mark Heverin (Register)
Caoife Madden
Laboratory/Neuropharm
Dr. Julie Kelly
Dr. Alice Vajda
Gill Slator
Health Services
Prof.Anthony Staines
Prof.Charles Normand
Dr. Miriam Galvin
Dr.Shelagh Connolly
Dr.Katy Tobin
Dr.Padraig Ryan
Dr.Sinead Maguire
Rebecca Gaffney
Iain Mays
Brighid Gavin
EMG & Biomarkers
Dr.Ger Mullins
Dr.Taha Omar
Genetics
Clinical Trials
Prof Dan Bradley
Dr.Russell McLaughlin
Dr. Kevin Kenna
Liz Fogarty
Dr.Sam Bouazzaoui
Dr.Sinéad Maguire
Academic Neurology
Dominique Plant
Research Managers
Dr.Alice Vajda
Mark Heverin
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
RESEARCH FUNDING