Evdokia Anagnostou, MD
Clinician Scientist, Holland Bloorview Kids Rehab Hospital
Associate Professor, Department of Pediatrics
University of Toronto
Canada Research Chair in Translational Therapeutics
The challenge
• > 300,000 children and youth in Ontario with
neurodevelopmental disorders (NDs):
– Autism Spectrum Disorders (ASD), Attention Deficit
Hyperactivity Disorder (ADHD), Obsessive
Compulsive Disorders (OCD) and Intellectual
Disability (ID).
• Lifetime cost per individual as high as $2 million
in Canada
• Ability to change long term outcomes remains
limited
The challenge
• Few medications to treat these disorders
– Almost none have been discovered by translating the
findings from basic sciences such as genomics, animal
models, pathology etc.
• There are many reasons why development of novel treatments
for NDs has been limited:
e.g.
– It is difficult to stratify patients into those most likely to
respond to the intervention
– Few molecular targets
– There are no established networks of excellence to
rapidly screen compounds and advance promising
compounds
POND
• An integrated discovery system to expedite
– understanding biology
– Translation into novel therapeutics
• Across developmental disorders
• 4 research sites: HBKRH, SickKids, McMaster, Western
• >20 investigators, 40 clinicians
• >15 industry partners and advocacy organizations
The plan
• Create the first clinical trials network
dedicated to neurodevelopmental
disorders in Canada
– Existing expertise in NDs
– Enhancing regulatory expertise
– Go where the children are
The plan
• Embed the OCTN in a large biomarker core
– clinical database of children and youth with NDs
• properly characterize with behavior, cognition
• Characterize biology
– imaging and electrophysiology techniques
– Genomics (leveraged) and epigenomics
The plan
• In parallel:
– Develop animal and cellular models
• better understand disease mechanisms by crossanalyzing data from the human subjects with mouse and
cell modelling results
• enable testing of medications for response and safety
before they are used in children.
Database / Biomarker core
• Currently: >1000 children with ASD,
ADHD, OCD ,ID
– Core technologies used for characterization:
• Detailed behavioural characterization
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–
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Stage 1: demographics
Stage 2 : cross disorder phenotyping
Stage 3: In depth diagnostic phenotyping
Stage 4: Cognitive phenotyping
• Genomics (leveraged)
• Imaging ~200 imaged children
• Electrophysiology (MEG, ERP/EEG, autonomic
nervous system markers)
Highlights
Results: Electrodermal activity (EDA)
Results: Effect of anxiety
Future Directions
* As of summer 2014:
Specific commitment to:
Tourette Syndrome
Down syndrome
Fragile X
Rett syndrome
• NEW RFA for pilot studies, due Summer 2015
• New compound for next clinical trial secured: GSK3b
inhibitor
• Thank you