# Clinical Validation of Serum Neurofilament Light as a Biomarker of Traumatic Axonal Injury

> **NIH NIH U01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $778,501

## Abstract

Project Summary/Abstract: Traumatic brain injury (TBI) is one the leading causes of mortality and morbidity
affecting humanity, and a recognized risk factor for late-life neurodegenerative disorders. The absence of
validated biomarkers in the neurotrauma field is a barrier to drug development in this area, and as a
consequence there are currently no disease-modifying therapies that limit the burden of TBI. TBI is a complex
disease process, and there is a need to identify and measure subtypes of injury, in order to develop precision
medicine approaches where specific pathobiological processes are targeted by mechanistically appropriate
therapies. Traumatic axonal injury (TAI) is a common pathologic consequence of TBI, and underlies some of
the most disabling consequences of injury, including cognitive and affective problems. Recent breakthroughs in
pre-clinical models indicate that novel therapeutic interventions are effective in promoting resilience of injured
axons and improving neurologic outcome after experimental TBI. Translation of such promising therapies into
successful clinical trials will require prognostic biomarkers that can measure TAI in individual patients, so they
can be selected for early phase studies of axono-protective therapies, as well pharmacodynamic biomarkers
than can measure the biologic efficacy of such treatments. Currently, the best biomarker for TAI is fractional
anisotropy (FA) and mean diffusivity (MD) of white matter tracts, measured using diffusion tensor imaging (DTI)
MRI. This technique, while robust, is poorly suited for dynamic longitudinal assessments, and measures the
end-result of axonal degeneration, rather than an early step in the neurodegenerative process. Recently, the
ability to assay axonal proteins in peripheral blood has made it potentially feasible to assess of TAI rapidly,
inexpensively, and longitudinally. The axonal protein that holds the most promise as a marker of axonal
degeneration is neurofilament light chain (NF-L). We hypothesize that NF-L is a prognostic biomarker of TAI.
Our project has 3 specific aims:
 Specific aim 1. We will determine reference intervals (RIs) for NF-L according to Clinical Laboratory
Standards Institute (CLSI) guidelines, using commercially available assays (Quanterix, LLC, Lexington, MA).
 Specific aim 2. We will measure NF-L in existing serum samples from participants enrolled in a multi-center
observational study (TRACK-TBI) who also have MRIs at 2 weeks and 6 months after injury. The relationship
between NF-L elevations and neuroimaging measures of TAI (DTI measure of FA at the 2-week scan) and axonal
degeneration (white matter volume at 6 months after injury) will be assessed.
 Specific aim 3. We will extend the follow-up period of a subset of TRACK-TBI participants from 1 year to 5
years after injury, to assess the relationship between persistent NF-L elevations and neurodegeneration. The
existing clinical, imaging, and biomarker data in these subjects will b...

## Key facts

- **NIH application ID:** 9873707
- **Project number:** 1U01NS114140-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ramon Diaz-Arrastia
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $778,501
- **Award type:** 1
- **Project period:** 2020-03-15 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873707

## Citation

> US National Institutes of Health, RePORTER application 9873707, Clinical Validation of Serum Neurofilament Light as a Biomarker of Traumatic Axonal Injury (1U01NS114140-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873707. Licensed CC0.

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