# Development of myelinating oligodendrocytes in Down syndrome

> **NIH NIH R21** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $247,500

## Abstract

The list of developmental events that may lead to intellectual disability in Down syndrome (DS) ranges from
the over expression of single genes to altered synaptic and firing properties of neurons throughout the nervous
system. Recently, our laboratory has discovered intrinsic defects in oligodendrocyte precursor cell (OPC)
maturation that lead to changes in myelination and white matter tract formation in a mouse model of DS. This
dysmyelination, confirmed using human brain gene expression profiling and myelin imaging, has been shown
to lengthen the time it takes for action potentials to reach their postsynaptic targets. Since this novel cellular
defect presumably underlies at least part of the intellectual disability in DS, a straightforward therapeutic
approach would be to treat with compounds that promote OPC maturation. Initial results in mouse models look
promising, but whether OPCs from humans with DS exhibit the same defects found in mouse model cells is
critical for this effort.
In this project, we will take advantage of pre-existing human stem cell lines and rapid OPC programming
protocols to evaluate the maturation of human DS-derived OPCs for the first time. Next, in a series of in vitro
experiments, we will test two FDA-approved drugs for their ability to prompt OPC differentiation and then test
their myelination potential by transplanting these cells into the myelin-deficient Shiverer mouse brain. The
results of these studies will generate a novel cellular resource for future study in the DS field, test the
hypothesis that human DS-derived OPCs exhibit the same defects found in mouse model cells, and evaluate
the efficacy of two potential drugs that could be used to improve myelination in the brains of people with DS.

## Key facts

- **NIH application ID:** 9975899
- **Project number:** 5R21HD098542-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** ELLA ZELDICH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $247,500
- **Award type:** 5
- **Project period:** 2019-07-11 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975899

## Citation

> US National Institutes of Health, RePORTER application 9975899, Development of myelinating oligodendrocytes in Down syndrome (5R21HD098542-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9975899. Licensed CC0.

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