# Plasma metabolite and proteome signatures for migraine classification

> **NIH NIH R61** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $2,065,041

## Abstract

Project Summary/Abstract
 Migraine is a debilitating pain condition and ranks globally in the top five for years lived with disability.
Approximately 15% of the general US population experiences migraine, with women afflicted approximately
twice as often as men. Migraine is currently diagnosed by a qualifying recurrence of symptoms, including aura,
formally codified by the International Classification of Headache Disorders. However, the lack of established,
explicitly quantitative biomarkers for migraine, especially causal biomarkers, is widely viewed as a critical
impediment to optimizing and developing therapeutic strategies, and to advancing understanding of migraine
pathophysiology. Our preliminary data suggest that such causal plasma-based biomarkers exist and can be
identified. In addition, formally diagnosed migraine may present with or without aura and a diversity of other
symptoms, all equally qualifying for migraine, suggesting heterogeneity in migraine etiology. Thus, a second
but equally important goal for a quantitative migraine biomarker, especially a causal biomarker, is to resolve
possible subclasses of migraine, which may be used in treatment decisions.
 We propose an investigation that is responsive to PAR-19-315 through a goal of identifying and
validating plasma-based biomarkers diagnostic of migraine and its potential subclasses. During the R61 phase
of the research, we will measure a comprehensive panel of >1300 plasma metabolites and 92 vascular related
proteins among three groups of women from the Women’s Genome Health Study (WGHS): those with active
migraine, non-migraine headache, and no headache symptoms. In these data, we will use state-of-the-art
statistical modeling to identify plasma-based metabolite and protein signatures of migraine that formally
discriminate individuals with active migraine from those never reporting headache and also those reporting
non-migraine headache as well as among sub-classes of migraine defined by specific migraine symptoms, e.g.
aura. Using existing genetic data, we will apply a genetic instrumental variable method termed “Mendelian
Randomization” to assess whether these metabolite signatures may have causal effects on migraine. During
the R33 phase, we will develop and apply a validated assay(s) targeting the metabolite(s) and/or protein(s)
identified in the R61 to perform an initial validation study our biomarker signature within a new cohort of men
and women recruited for this project.
 We anticipate that findings from the proposed research have the potential to help refine the analysis of
response in clinical trials, optimize current prophylactic strategies, suggest new therapeutics, and resolve
uncertainty in assignment of diagnostic aura status and other potential sub-classes of migraine.

## Key facts

- **NIH application ID:** 10219629
- **Project number:** 1R61NS122074-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Daniel Ian Chasman
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,065,041
- **Award type:** 1
- **Project period:** 2021-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219629

## Citation

> US National Institutes of Health, RePORTER application 10219629, Plasma metabolite and proteome signatures for migraine classification (1R61NS122074-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10219629. Licensed CC0.

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