# Blood Test to Aid Treatment Decisions for Perinatal Asphyxiation

> **NIH NIH U01** · MESO SCALE DIAGNOSTICS, LLC · 2021 · $828,886

## Abstract

This industrial-academic collaboration seeks to analytically validate a highly specific and sensitive
multiplexed immunoassay for glial fibrillary acid protein (GFAP) and tau in serum and/or plasma to improve
treatment decisions for neonates with hypoxic-ischemic encephalopathy (HIE). HIE, which affects
approximately 1 in every 1,000 births, is a major cause of death and disability for children. Prompt whole body
cooling of neonates improves outcomes in some cases; however, 24% of cooled neonates die from HIE, and
19% of survivors develop cerebral palsy despite best available treatment. Adjuvants to hypothermia promise
to broaden the effectiveness of treatment. Clinical testing of these investigational adjuvants has been slow due
to the difficulty in identifying neonates who are most likely to benefit from treatment. By prescreening neonates
at the extremes of the injury spectrum, an objective simple blood test that stratifies neonates according to
injury severity and monitors treatment responses would accelerate trials of investigational adjuvants.
 The multiplex employs a novel format with approximately 100-1,000x higher sensitivity than regular
immunoassays, which improves quantitation in the clinically relevant ranges of these low abundance
biomarkers. Our preliminary data demonstrate that our new assay format is sufficiently sensitive to measure
GFAP and tau in serum and plasma. Collaborators at Johns Hopkins University (Drs. Everett and Northington)
have demonstrated clinical utility of GFAP and tau as markers of injury severity and functional outcomes in
HIE. This proposal seeks to fully develop and optimize the ultrasensitive multiplex using our phase-gated
process, followed by extensive analytical validation.
 First-year tasks are extensive characterization of key critical reagents, assay fine-tuning, and establishment
of analytical controls at key concentrations for stratifying neonates according to HIE severity. A risk analysis
will be performed, and the effect of preanalytical factors and potential interferents will be assessed and
mitigated. In year two, the design will be frozen and transferred to manufacturing. QC protocols for critical
reagents will be established and executed, and components will be configured following MSD’s ISO
9001:2015-certified quality management system. Three kit lots at final design will be manufactured. Assay
performance will be assessed throughout the project, and include testing of clinical samples. A formal
analytical assay validation plan will be developed in collaboration with a clinical chemist (Dr. Sokoll from JHU),
with input from the NIH Program Officers, and based on the 2018 FDA Bioanalytical Method Validation
Guidance for Industry. The final analytical validation study will be performed at three sites: MSD, Johns
Hopkins Hospital, and All Children’s Hospital. Multi-site testing will include testing of proficiency samples, a
20-day reproducibility study, and a lot-to lot comparison. Additionall...

## Key facts

- **NIH application ID:** 10073558
- **Project number:** 5U01NS114144-02
- **Recipient organization:** MESO SCALE DIAGNOSTICS, LLC
- **Principal Investigator:** Christopher T. CAMPBELL
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $828,886
- **Award type:** 5
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073558

## Citation

> US National Institutes of Health, RePORTER application 10073558, Blood Test to Aid Treatment Decisions for Perinatal Asphyxiation (5U01NS114144-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10073558. Licensed CC0.

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