Rare Disease Day 2016 Conference March 9 - 10: Day 1

1. Canada's rare disease
research pla/orms
Kym Boyco5 PhD, MD, FRCPC, FCCMG
Clinical Gene*cist, Children’s Hospital of Eastern Ontario
Senior Scien*st, CHEO Research Ins*tute,
Professor of Pediatrics, University of O@awa

2. 2
This is a short story about…
2 2
Unmet Medical Need
• Diagnosis is Care
• Therapies

3. Dr. Gudrun Aubertin
Dr. Jan Friedman
Dr. Francois Bernier
Dr. Ordan Lehman
Dr. Bridget
Fernandez
Dr. Sarah Dyack
Dr. Edmond
Lemire
Dr. Albert
Chudley
Dr. Victoria Siu
Dr. Malgorzata Novaczyk
Dr. Linda Kim
Dr. Peter Kannu
Dr. David Chitayat
Dr. Rosanna Weksberg
Dr. Marjan Nezarati
Dr. Sarah Nikkel
Dr. Sandra Farrell
Dr. Jacques Michaud
Dr. Sebastian Levesque
Dr. Régen Drouin
Dr. Bruno Maranda
Canadian Network
2010 and in 2 weeks…

4. 4
Addressing the grand challenge
4 4
Rare Pediatric
Disease Gene
Discovery
Disease
Phenotyping and
Mechanism
TherapeuLc
Discovery and
ValidaLon
>4000
rare
disease
samples
90
mechanism
projects
>200 rare
diseases
to enter
pipeline
$20M in opera*ng funds
$20M in infrastructure

5. Project Teams
-validation
studies-
National Data
Coordination Centre
-data sharing-
Vancouver
Toronto
Montreal
STICs
-exome
sequencing-
Share resources and expertise

6. Rare Disease Gene Discovery
1. Orchestrated RD pipeline
>1300
Diseases
Proposed
>1000
Diseases
Selected for
Study

7. 417 disorders out of pipeline …
56%
Solved
Am J Hum Genet 2014; 94:809-817
Novel
71
Known
161

8. 417 disorders out of pipeline …
56%
Solved
Am J Hum Genet 2014; 94:809-817
Novel
71
Known
161

9. CCMG guidelines:
DiagnosLc translaLon
Journal of Medical Genetics 2015

10. 417 disorders out of pipeline …
56%
Solved
Am J Hum Genet 2014; 94:809-817
Novel
71
Known
161

11. genomicsandhealth.org
N-of-1
PaLent #1
Clinical GeneLcist #1
PaLent #2
Clinical GeneLcist #2
Genotypic Data
Gene A
Gene B
Gene C
Gene D
Gene E
Gene F
Phenotypic
Data
Feature 1
Feature 2
Feature 3
Feature 4
Feature 5
Genotypic
Data
Gene D
Gene G
Gene H
Phenotypic
Data
Feature 1
Feature 3
Feature 4
Feature 5
Feature 6
Genomic
Matchmaker

12. › >1700 cases
phenomecentral.org
includes data from:
› >500 users
PhenomeCentral

13. Currently Connected MME Services
Test set of 50
solved cases into
all connected
databases
All come back!!

14. 2. Orchestrated RD pipeline
Cell
Models
Yeast
Models
Zebra
fish
Models
Mouse
Models
Disease phenotyping and mechanism
‘Omics Profiling
High-content imaging
Mutation
Gene
Protein
Pathway
Disease
expertise
Triaging

15. h@p://rare-diseases-catalyst-network.ca/

16. RD Models and Mechanisms Network
GeneX
$25K
$2.3 M Catalyst Grant
30 Catalyst Grants Awarded to Date

17. 3. Orchestrated RD pipeline
Screening
FDA-approved
pharmacopeia
Pharma’s
shelved Phase
II assets
Druggable
target
iden*fica*on
Yeast
RNAi
Drug lead
valida*on in
model
systems
Protein-Drug
Interac*ons
Discovery
TherapeuLc Discovery and ValidaLon
ValidaLon

18. Re-posiLoning of clinic-ready compounds
Glut 1
Farber
Dravet
SCA15
Fronto-
temporal
dementia
MAPT CMT1B
Spondylo
epiphysea
l dysplasia
tarda
HSP
Type 4
Cerebellar
atrophy
short
stature
Familial
Hemiplegic
Migraine
type 2
Optic
atrophy
type 1
Loeys-Dietz
syndrome
Creatine
transporter
deficiency
Dysferlinopathies
HSP54 D-bifunctional
protein deficiency
SCA28
Benign
chronic
pemphigus
ARSACs
POLR3A
Leuko
diverse opportuni-es
Drug targets
Corresponding mRNA of the RD
Cellular phenotype of the RD

19. Canadian community
Teamwork
Shared
resources
Common goal
Closely
linked

21. And it’s all about…
Changing healthcare
through cost effecLve
diagnosis tests for RDs
IdenLficaLon and
advancement of
therapeuLc opportuniLes