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Canada'srarediseaseresearchpla/orms
KymBoyco5PhD,MD,FRCPC,FCCMGClinicalGene*cist,Children’sHospitalofEasternOntario
SeniorScien*st,CHEOResearchIns*tute,ProfessorofPediatrics,UniversityofO@awa
2
Thisisashortstoryabout…
22
UnmetMedicalNeed• DiagnosisisCare• Therapies
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
CanadianNetwork
2010andin2weeks…
4
Addressingthegrandchallenge
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RarePediatricDiseaseGeneDiscovery
DiseasePhenotypingand
Mechanism
TherapeuLcDiscoveryandValidaLon
>4000 rare
disease samples
90 mechanism
projects
>200 rare diseases to enter pipeline
$20Minopera*ngfunds$20Mininfrastructure
Project Teams -validation studies-
National Data Coordination Centre
-data sharing-
Vancouver
Toronto
Montreal
STICs -exome
sequencing-
Share resources and expertise
RareDiseaseGeneDiscovery
1.OrchestratedRDpipeline
>1300DiseasesProposed
>1000Diseases
SelectedforStudy
417disordersoutofpipeline…
56% Solved
Am J Hum Genet 2014; 94:809-817
Novel 71
Known 161
417disordersoutofpipeline…
56% Solved
Am J Hum Genet 2014; 94:809-817
Novel 71
Known 161
CCMGguidelines:
DiagnosLctranslaLon
Journal of Medical Genetics 2015
417disordersoutofpipeline…
56% Solved
Am J Hum Genet 2014; 94:809-817
Novel 71
Known 161
genomicsandhealth.org
N-of-1
PaLent#1ClinicalGeneLcist#1
PaLent#2ClinicalGeneLcist#2
GenotypicDataGeneAGeneBGeneCGeneDGeneEGeneF
PhenotypicData
Feature1Feature2Feature3Feature4Feature5
GenotypicData
GeneDGeneGGeneH
PhenotypicData
Feature1Feature3Feature4Feature5Feature6
GenomicMatchmaker
› >1700 cases
phenomecentral.org
includes data from:
› >500 users
PhenomeCentral
CurrentlyConnectedMMEServices
Testsetof50solvedcasesintoallconnecteddatabases
Allcomeback!!
2.OrchestratedRDpipeline
CellModels
YeastModels
Zebrafish
Models
MouseModels
Diseasephenotypingandmechanism
‘OmicsProfiling
High-contentimaging
Mutation Gene Protein Pathway Disease expertise
Triaging
h@p://rare-diseases-catalyst-network.ca/
RDModelsandMechanismsNetwork
GeneX
$25K
$2.3MCatalystGrant
30 Catalyst Grants Awarded to Date
3.OrchestratedRDpipeline
ScreeningFDA-approvedpharmacopeia
Pharma’s
shelvedPhaseIIassets
Druggabletarget
iden*fica*on
YeastRNAi
Drugleadvalida*onin
modelsystems
Protein-DrugInterac*ons
Discovery
TherapeuLcDiscoveryandValidaLon
ValidaLon
Re-posiLoningofclinic-readycompounds
Glut 1
Farber Dravet
SCA15
Fronto-temporal dementia
MAPT
CMT1B
Spondylo epiphyseal 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
diverseopportuni-es
DrugtargetsCorrespondingmRNAoftheRDCellularphenotypeoftheRD
Canadiancommunity
Teamwork Sharedresources
Commongoal
Closelylinked
Andit’sallabout…
ChanginghealthcarethroughcosteffecLvediagnosistestsforRDs
IdenLficaLonandadvancementoftherapeuLcopportuniLes