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

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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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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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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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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