Rare Disease Research in Canada: Building on Success

Paul Lasko, Scientific Director, CIHR Institute of Genetics

Rare disease research has been funded through a larger Personalized Health Initiative Personalized Medicine Initiative

•  Enhance  health  outcomes  through  pa1ent  stra1fica1on  approaches  by  integra1ng  evidence-­‐based  medicine  and  precision  diagnos1cs  into  clinical  prac1ce  

•  $240M  ($85M  from  CIHR)  •  110  compe11on  and  applica1on  

partners,  including  Genome  Canada  

2  

•  Drive  evidence-­‐based  implementa1on  of  PH  that  will  iden1fy  solu1ons  that  can  contribute  to  more  cost-­‐effec1ve  and  sustainable  healthcare  

•  CIHR’s  investments  currently  planned  :  $45M  

•  Alignment  with  IC  PerMed  

Personalized Health Initiative

2012   2016  

eHealth Innovation Initiative

•  Enhance  health  outcomes  and  health  care  delivery,  through  the  implementa1on,  evalua1on  and  scale-­‐up  of  eHealth  innova1ons  

•  $34.4M  ($16.2M  from  CIHR)  •  77  applica1on  partners  

Canadian Success Stories 3  

•  Recruited  over  3000  pa1ents  and  family  members  to  study;  

•  Studied  637  different  rare  diseases;  •  Have  provided  a  diagnosis  to  over  1000  

pa1ents;  •  Have  iden1fied  85  novel  rare  disease  

genes;  •  Are  developing  three  experimental  

therapies;  •  Contribute  to  interna1onal  data  sharing  

standards.  

•  Interna1onal  consor1um  grouping  samples  and  exper1se  on  high  grade  astrocytomas  

•  Iden1fied  recurrent  driver  muta1ons  affec1ng  DNA  structure,  now  part  of  WHO  test  recommenda1ons  

•  Developed  an  oncopanel  now  used  in  clinical  trials  and  CLIA  cer1fied  

 

GeneX  

$25K  

$2.3  M  Catalyst  Grant  

Network Catalyst Grant: “Canadian Rare Diseases : Models & Mechanisms Network” Objectives: 1.  Enable collaboration between clinician scientists (rare disease gene discovery)

and basic scientists (expertise in the the cognate gene’s function)

2.  Determine the functional consequences of the mutations found (validate protein loss of function or altered function) coincident with discovery

3.  Provide seed funding ($25K) to the collaborating scientists to obtain functional data for publication or as preliminary results for a larger grant application

4.  Develop an information portal for resources, databases, technologies, core facilitites, etc. available in Canada

For more information see Hieter and Boycott (2014) Genetics 198: 443-445.

Clinical Gene Discovery Applicants

Model Organism Investigators

Register to Join the Network

Generate Functional Data

Give Insights into Disease Pathogenesis

Validate Clinical Gene Discoveries

Suggest Therapeutic Targets

Entry Points

Foster Longer Standing Collaborations

Decision Points Connections Destinations

Submit a Connection Application

Clinical Advisory

Committee

Scientific Advisory

Committee Catalyst Grants

Registry

Network Routemap

From the RDM website (have a look!) http://rare-diseases-catalyst-network.ca

The  RDMM  has  generated  a  huge  amount  of  interest…  

Ac1vity  data  as  of  4  Nov  2016  

Ar1cle  about  RDMM  in  Nature  Medicine  (2015)  21:  1242-­‐3  

…and  great  research!  

Nature  Gene.cs  (2016)  48:  777-­‐784,  acknowledges  RDMM  support  

Matchmaker  Exchange:    The  Next  Genera1on  

Kym  Boyco>,  PhD,  MD,  FRCPC,  FCCMG  Professor  of  Pediatrics,  University  of  Oaawa  On  behalf  of  MME  Working  Group  

Currently  Connected  MME  Services  

Federated  Network  

As  of  2016  

•  Australia  –  Western  Australian  Department  of  Health  

•  Canada  –  Canadian  Ins1tutes  for  Health  Research  –  Genome  Canada  

•  China  –  Beijing  Genomics  Ins1tute  –  Chinese  Rare  Disease  Research  Consor1um  –  WuXi  Apptec  

•  EU  –  European  Commission  

•  Finland  –  Academy  of  Finland  

•  France  –  French  Associa1on  against  Myopathies  –  Agence  Na1onal  de  la  Recherche  –  Lysogene  –  EORTC  

•  Georgia  –  Children’s  New  Hospital  Management  Group  

•  Germany  –  Federal  Ministry  of  Educa1on  and  Research  

•  Italy  –  Italian  Higher  Ins1tute  of  Health  –  Telethon  Founda1on  –  Chiesi  Farmaceu1ca  

•  Interna1onal  Consor1um  –  E-­‐RARE  3  Consor1um  

•  Japan  –  Japan  Agency  for  Medical  Research  and  Development  –  Na1onal  Ins1tutes  of  Biomedical  Innova1on,  Health,  and  Nutri1on    

•  Republic  of  Korea  –  Korean  Na1onal  Ins1tute  of  Health  

•  Netherlands  –  The  Netherlands  Organiza1on  for  Health  Research  and  

Development  –  Prosensa  

•  Kingdom  of  Saudi  Arabia  –  Saudi  Human  Genome  Project  

•  Spain  –  Na1onal  Ins1tute  of  Health  Carlos  III  

•  UK  –  Na1onal  Ins1tute  for  Health  Research  

•  USA  –  Food  and  Drug  Administra1on  Orphan  Products  Grants  

Program  –  Isis  Pharmaceu1cals  –  Na1onal  Human  Genome  Research  Ins1tute  (NIH)  –  Na1onal  Center  for  Advancing  Transla1onal  

Sciences(NIH)  –  Na1onal  Cancer  Ins1tute  (NIH)  –  Na1onal  Eye  Ins1tute  (NIH)  –  Na1onal  Ins1tute  of  Neurological  Disorders  and  Stroke  

(NIH)  –  Na1onal  Ins1tute  of  Arthri1s  and  Musculoskeletal  and  

Skin  Diseases  (NIH)  –  Na1onal  Ins1tute  of  Child  Health  and  Human  

Development  (NIH)  –  NKT  Therapeu1cs  –  Office  of  Rare  Diseases  (NIH)  –  PTC  Therapeu1cs  –  Sanford  Research  Ins1tute  

•  Interna1onal  Pharma  Companies  –  Genzyme  (Sanofi)  –  Novar1s  –  Pfizer  –  Shire  

Progress  toward  IRDiRC’s  goals  (source:  www.irdirc.org)  

•  Diagnos1cs  (goal:  most  rare  diseases  by  2020)    – Nearly  3,600  rare  diseases  for  which  there  is  a  gene1c  test  available,  as  compared  with  2,200  in  2010.  

•  Therapies  (goal:  200  new  therapies  by  2020)  – 195  as  of  May  2016.