1. Programmatic Research on Fetal Alcohol Spectrum Disorder (FASD)
Presentation to the
Child Health Signature Research Program Group
February 21, 2008
Daniel Savage, Ph.D.
Regents’ Professor & Chair
Department of Neurosciences, UNM SOM 3

2. Fetal Alcohol Spectrum Disorder ( FASD )
Physical Defects
FAS ~ 0.03%
FAE / ARBD ~ 0.15%
Alcohol-Related
Neurodevelopmental
Disorder (ARND) > 1%
Functional Deficits

3. Long-Term Research Objectives
Understand the neurobiologic bases of fetal ethanol-induced deficits in synaptic plasticity and learning.
Identify therapeutic agents that ameliorate fetal ethanol-induced deficits in synaptic plasticity and learning.
Establish combined neurobehavioral and functional neuroimaging approaches for:
Diagnosis of fetal ethanol-associated brain and behavioral deficits and,
Monitoring / predicting the efficacy of various behavioral and pharmacotherapeutic agents.
Identify a sensitive and specific biomarker system predictive of adverse neurobehavioral outcomes in fetal ethanol-exposed offspring. 3

4. Identify therapeutic agents that ameliorate fetal ethanol induced synaptic plasticity & learning deficits. (R21 AA16619)
Concept: Use of our moderate ethanol exposure paradigm as a screen for identifying therapeutic agents for treating cognitive deficits associated with prenatal ethanol exposure.
Approach: “Proof of Concept” proposal to study one cognition-enhancing agent, a selective H3 receptor antagonist ABT-239.
One-trial Contextual Fear Conditioning
Four-day Retention of Platform Location

5. Virtual Morris Water Task
Neurobehavioral and functional neuroimaging characterization of learning deficits in subjects with FASD (MIND C-2018)
Virtual Morris Water Task
Volumetrics
Spectroscopy
Phase II: Probe Trial
MEG
Control:
6 / 7
FAS:
1 / 7

6. 4. A biomarker system for predicting adverse neurobehavioral
4. A biomarker system for predicting adverse neurobehavioral outcomes in fetal ethanol-exposed offspring. (R21 AA15420)
Employ our moderate prenatal ethanol exposure paradigm to examine ethanol-induced alterations in placental protein expression using proteomic and genomic approaches.
302 genes (0.13% of all genes) were altered greater than two-fold by moderate maternal ethanol consumption
Genes whose proteins associated with cytoskeletal, metabolic, endocrine, immune or neural function are altered.
Follow-up Studies:
1. “Sensitivity Studies” Ethanol Dose Window of detectability
2. “Specificity Studies” Other risk factor impact
Preclinical
Clinical
Placental
Proteomics
Placental
Proteomics
Fetal Brain
Proteomics
Weanling
Behaviors &
Neurophysiology
Infant
Behaviors &
Neurophysiology 3

7. Developmental Alcohol Research Center - P20
Fetal ethanol-induced behavioral deficits: Mechanisms, diagnoses and interventions
Preclinical Projects:
Epigenetics of FASD
Stem Cells
Cognition Enhancers
Predisposition to PTSD
Biomarkers Diagnosis / Prognosis
Preclinical Investigators: Allan, Caldwell, Cunningham, Hamilton, Perrone-Bizzozero, Savage, Valenzuela, Zhao
Clinical Projects:
Information Processing
Infant Sensory Integration (baby MEG)
Behavioral Intervention & Functional Neuroimaging
Clinical investigators: Kodituwakku, Verney, Stephen, Tesche, Kiehl, May, Rayburn, Weisend
Developmental Alcohol Research Center - P20
Combines basic, clinical and translational science across HSC, Main Campus and MIND