Canada'srarediseaseresearchpla/orms

KymBoyco5PhD,MD,FRCPC,FCCMGClinicalGene*cist,Children’sHospitalofEasternOntario

SeniorScien*st,CHEOResearchIns*tute,ProfessorofPediatrics,UniversityofO@awa

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Thisisashortstoryabout…

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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…

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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