# Vasculature provides the substrate for oligodendrocyte progenitor migration in development and disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $346,719

## Abstract

PROJECT SUMMARY/ ABSTRACT
In demyelinating diseases such as multiple sclerosis (MS) and Periventricular Leukomalacia associated with
Cerebral Palsy (CP), myelin sheaths are lost through injury or death of oligodendrocytes (OL). Remyelination
by oligodendrocyte precursor cells (OPCs) is considered crucial to recovery, but myelin repair often fails
contributing significantly to ongoing neurological dysfunction, axonal loss and disease progression. There are
currently no therapies to promote remyelination, and one of the greatest unmet needs is gaining a greater
understanding of the obstacles to successful myelin repair. Remyelination can be divided into two critical
stages: Firstly (1) recruitment of migrating OPCs into areas of demyelination from surrounding normal
appearing white matter followed by (2) their differentiation into mature OL within the lesion. We have recently
identified that OPCs migrate during their developmental dispersal around the CNS using vasculature as a
physical scaffold for motility (Science 351, 379 (2016)). This requires movement along vessels, but also
subsequent detachment from vasculature after migration to allow OPC differentiation. The mechanism of
migration of OPCs into remyelinating lesions, critical for successful myelin repair, remains largely unclear. This
grant will (1) identify for the first time how OPCs are recruited into remyelinating lesions utilizing
vasculature as a physical scaffold for motility. It will (2) demonstrate that failure of OPCs to detach
from vasculature appropriately is a pathological finding in human white matter injury. It will identify
this inability to detach not only as a mechanism preventing their proper distribution into lesions but
also as an obstacle for subsequent OPC differentiation. (3) It will show that OPCs remaining
inappropriately attached to vessels interfere with astrocyte-vascular coupling and integrity of the
blood brain barrier that may contribute further to lesion pathology.

## Key facts

- **NIH application ID:** 9869946
- **Project number:** 5R01NS097551-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Stephen Philip James Fancy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $346,719
- **Award type:** 5
- **Project period:** 2017-03-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869946

## Citation

> US National Institutes of Health, RePORTER application 9869946, Vasculature provides the substrate for oligodendrocyte progenitor migration in development and disease (5R01NS097551-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9869946. Licensed CC0.

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