B. Keith English, M.D. Chair, Pediatrics & Human Development Michigan State University 10/29/2015

1. B. Keith English, M.D.
Chair, Pediatrics & Human
Development
Is Precision Medicine a Pipe Dream?

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Why “Precision” Medicine?
 Personalized, individualized, or precision
medicine?
 For some, “personalized medicine” denotes
the creation and use of unique therapies for
every patient, whereas “precision medicine”
refers to the “tailoring of medical treatment to
the individualized characteristics of each
patient” (National Research Council, 2011)

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 Why is precision medicine in
pediatrics a priority?

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Fit with Grand Initiatives and
NIH Funding Priorities
 Fit with NICHD Funding Priorities for the next
decade:
– “Catalog and identify interrelated environmental and
genetics factors that are key to .. health”
– Focus areas include developmental origins of health
and disease & behavior and cognition (interventions for
autism and pharmaceutics for brain recovery)
– Fit with the NIH/DARPA/NSF “Brain Initiative”
– Fit with with National Human Genome Research
Institute (NHGRI) funding priorities

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Fit with MSU Multi-Campus
model for pediatric research
 Fit with dramatic expansion of pediatric
neurology, epilepsy and neuroscience in
Grand Rapids in partnership with HDVCH (&
with epigenetics at VARI)
 Fit with expanding programs in autism-related
research in Pediatrics in East Lansing
 Fit with public health expansion in Flint
 Fit with new CHM investigators in Traverse
City (autism), Marquette, Midland, Southfield

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Key Partners for “Precision
Pediatrics”
(1) Omics/Big Data Scientists
(2) Physician-Scientists whose focus is on
genomics/transcriptomics/metabolomics of major
medical conditions in children (e.g.,
Autism/Neurodevelopmental Disabilities/Epilepsy;
Childhood cancers; Asthma)
(3) Health Services Researchers whose aim is to
bring Precision Pediatrics to populations of children
with focus on PREVENTION

7. Potential Impact of Precision
Medicine in Pediatrics
 Autism:
– 15-20% of siblings of children with Autism
Spectrum Disorder will develop autism – but 80-
85% will not
– If we could identify the 15-20% early on, we could
target interventions designed to prevent or
ameliorate autism
– Genomics won’t be enough – we need
comprehensive omics and biomarkers for early
detection (? EEG, ? Transcriptome, Metabolome,
functional imaging?)
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8. Why autism needs precision
medicine
 Heritability now estimated at 70-80%
(twin studies from Sweden & King’s College London)
 Recent data suggest that up to 50% of
cases associated with de novo “likely gene
disruptive (LGD)” mutations – more likely
transmitted from mother; often involving genes
expressed during embryonic brain development
 Epigenetics also important – many
environmental factors affect fetal brain
development/autism risk (parental age, maternal
nutrition, maternal infections/inflammation, toxins, stress)
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9. Precision Interventions for
children with autism?
 Great frustration in the field – despite major
advances in understanding of role of many
genetic and environmental factors, this has not
translated into specific interventions
 Proof of concept greatly needed – targeted
intervention in specific subset of children with
or at risk for autism
 Rapamycin trial for children with tuberous
sclerosis and autism underway ..
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11. Potential Impact of Precision
Medicine in Pediatrics II
 Congenital CMV infection
– Affects 1/150 to 1/200 neonates in the U.S.
– Most asymptomatic at birth, but 10-15% of the
asymptomatically infected neonates will develop
significant hearing loss – yet 80-85% will not
– If we could identify the 10-15% who will develop
hearing loss early in life, we could target preventive
strategies and intensify followup (genomic,
epigenomic, metabolomic markers?)
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