1. Cerebral palsy genomics update
Michael Kruer, MD
CPRN Site PI, Phoenix
Chair, International Cerebral Palsy Genomics Consortium
CPRN Houston Investigators Meeting May 31-June 1, 2018

2. Aims & Hypotheses Identify genetic causes of CP
Why would we want to do that?
Challenge dogma- are we digging in the wrong place?
Precision Medicine: diagnosis & prognosis
Guide family planning
Preventative healthcare
Specific treatments
Better apply the tools we have

3. Who is doing this?

4. Methods
Recruit 500 parent-child trios with cryptogenic CP from CPRN centers
Enrollment via study coordinators; saliva collection kits (DNA source)
Phenotyping via CPRN Data Coordinating Center
Validate candidate CP genes in the
laboratory using cell lines and fly knockout models

5. Patient/Advocacy Engagement
“I just wanted to say how excited I am that you and your organisation are undertaking this project. For most of my life individuals with CP have been steeped in the narrative that there is very little to no ‘active’ science in CP and it made me feel very heartened (and a little emotional) to see that such care was being taken to investigate a very complex area.”
Amy Hogan, CP researcher/advocate (Y. Wilson, unpublished; used with permission)

6. Patient-centered outcomes
Questions
Do children with genetic forms of CP differ from those with environmental forms of CP? If so, how?
Can genetic forms of CP give us new insight into the disorder (as occurred in Parkinson and Alzheimer Disease)?
Genetic findings from this study can be returned to participants if they so choose

7. Subject population and sample size
All CPRN sites
This R01 focuses on “cryptogenic” CP (without known cause)
Sample size target: 500 families

8. Importance to CP community and fit with CPRN

9. Progress since concept review
R01 initial submission June 2017
Reviewed but not funded
Main critique #1: Statistical genomics analysis not robust enough
Main critique #2: Validation studies are lacking
Resubmission March 2018; in review
Addressed critique #1 by adding Peter Jin (Yale) and Qiongshi Liu (U Wisc)
Addressed critique #2 by adding validation studies initially proposed!

10. Call to action
Opportunity for a 2nd R01 submission comparing the genomic basis of cryptogenic and environmental CP
Both have a genetic basis! (Why do babies develop strokes or hemorrhages?!)
Plans for R21 assessing response to SDR in genetically-defined subtypes of CP (overlap with hereditary spastic paraplegia)

11. Questions?