# Astrocyte-specific exosomes as a platform for biomarker discovery in multiple sclerosis

> **NIH NIH R21** · YALE UNIVERSITY · 2023 · $209,375

## Abstract

Astrocyte-specific exosomes as a platform for biomarker discovery in multiple sclerosis.
Acute and chronic neuroinflammation are major drivers of MS pathology, which are difficult to quantify in vivo.
Thus, there is a significant unmet need for biomarkers that reliably reflect these processes. Astrocytes are highly
sensitive indicators of CNS pathology and active drivers of a wide range of pathological processes in MS. Like
most cells, astrocytes secrete a class of ultrasmall microvesicles termed exosomes. Because exosomal content
changes with the functional state of the parent cell, the cargo of astrocyte exosomes may provide a window into
the specific activation states of astrocytes. We have developed a strategy for isolating astrocytespecific
exosomes from patient plasma, based on the combined expression of glutamate/aspartate transporter (GLAST)
and glial fibrillary acidic protein (GFAP). In this proposal, we are exploring astrocyte-derived exosomes as a
platform for biomarker discovery in acute demyelination and secondary progression in MS. In specific aim 1, we
will comprehensively validate that GLAST+/GFAP+ exosomes are astrocyte-derived. In specific aim 2, we will
explore the utility of plasma-derived GLAST+/GFAP+ exosomes to provide biomarkers for two distinct MS
disease states – acute white matter demyelination and MS progression. To this end, we will profile the exosomal
miRNA content of MS patients with gadolinium-enhancing white matter lesions and with secondary progressive
MS and determine the miRNA signatures that are specific to each condition. Identifying exosome-based
biomarkers for lesion formation and MS progression would constitute a major advancement for MS patient care
and clinical trials. In follow-up studies, we will validate these biomarkers in larger MS patient cohorts.

## Key facts

- **NIH application ID:** 10645224
- **Project number:** 5R21NS129197-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** David Pitt
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $209,375
- **Award type:** 5
- **Project period:** 2022-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10645224

## Citation

> US National Institutes of Health, RePORTER application 10645224, Astrocyte-specific exosomes as a platform for biomarker discovery in multiple sclerosis (5R21NS129197-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10645224. Licensed CC0.

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