# Detection and Correction of Iron Deficiency Induced Abnormal Brain Metabolism

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $545,869

## Abstract

PROJECT SUMMARY/ABSTRACT
Long-term cognitive and behavioral deficits are the sequelae of iron deficiency (ID) prior to 3 years of age in
children. A causal relationship between early-life ID and brain dysfunction has been established in rodent
models, but not as clearly in humans due to a lack of peripheral biomarkers of brain iron status and function.
Using a nonhuman primate model that closely mimics human iron biology, brain development and metabolism,
we propose to discover novel biomarkers that index brain dysfunction in the pre-anemic stage of ID and
evaluate the efficacy of early iron treatment for mitigating ID-induced brain dysfunction. We will serially
measure from birth until 12 months, conventional hematological and iron-related indices, and novel proteomic-
and metabolomic-based biomarkers in the blood (serum) and intrathecal (CSF) compartments of ID infants and
iron sufficient control infants, concluding with neuroanatomical (MRI) and functional (behavior) assessments.
 Aim 1 will determine how best to employ serum proteomics and metabolomics to detect impending ID-
induced brain dysfunction by delineating which analytes and when in the course of ID, the serum proteome and
metabolome accurately reflect the brain metabolic, structural and functional impairments. We predict that
specific protein and metabolite changes reflecting distinct iron-regulated pathways will be detected in the
serum in the pre-anemic period and provide biomarkers of impending brain dysfunction. Aim 2 will quantify and
model the sensitivity of conventional hematological and serum iron parameters for detecting brain dysfunction
by serially monitoring these parameters relative to the metabolomic and proteomic indices of brain dysfunction
in concurrently obtained CSF. We predict that brain ID and dysfunction will be evident prior to the appearance
of anemia, indicating that hematological parameters used in clinical practice are insensitive as biomarkers of
brain iron and metabolic status. Aim 3 will test the hypothesis that iron treatment prior to anemia is essential
to mitigate the adverse neurological effects of ID. ID infants will be randomized to iron treatment either in the
pre-anemic stage of ID or after the development of anemia. The efficacy of the two therapies for restoring
hematological indices and brain iron status, metabolism, structure and function will be determined. We predict
that both treatments will normalize hematological indices, but only iron treatment begun in the pre-anemic
stage will fully restore brain iron status, metabolism, structure and function. This project is significant, because
it focuses on the benefits of early screening and interventions for improving the neurodevelopment of children
at risk for early-life ID. It is innovative because it will employ novel proteomic and metabolomic analyses to
simultaneously probe the blood and intrathecal compartments in a primate model that uniquely mimics the iron
and metabolic demands of th...

## Key facts

- **NIH application ID:** 9939594
- **Project number:** 5R01HD089989-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** CHRISTOPHER L COE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $545,869
- **Award type:** 5
- **Project period:** 2017-09-22 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939594

## Citation

> US National Institutes of Health, RePORTER application 9939594, Detection and Correction of Iron Deficiency Induced Abnormal Brain Metabolism (5R01HD089989-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9939594. Licensed CC0.

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