# MicroRNAs as critical regulators of remyelination in Multiple Sclerosis

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $346,719

## Abstract

Scientific Summary:
The purpose of this project is to identify the critical regulators of remyelination in multiple sclerosis (MS)
brains. It has been long established that oligodendrocyte progenitor cells (OPCs) populate MS lesions but do
not transform into mature oligodendrocytes (OL) for reasons that remain unresolved. Therefore, one of the
critical questions to ask is can we identify factors that prevent these cells from being able to mature and
remyelinate? In recent years, microRNAs (miRNAs) have been identified as critical regulators of gene
expression. We performed a comprehensive analysis of MS white matter lesions and identified 9 miRNAs that
target 12 genes associated with the maturation of OPCs into mature OLs. Aim 1 in the current proposal will
therefore validate these miRNAs and target genes in MS brains, specifically in grey matter. Aim 2 will build on
these findings and provide in vitro evidence of the capacity of these miRNAs to induce myelination in OPCs.
The next question to be answered is "does loss of miRNAs lead to decreased remyelination by halting the
progression of OPCs maturing into myelinating OLs in vivo? We propose to answer this question by using
mice with loss of the miRNA processing enzyme Dicer in mature OLs and in OPCs. The role of miRNAs in
promoting remyelination in vivo will be tested in Aim 3. The future of MS therapeutics lies in the identification of
additional therapeutic targets and in developing combinatorial strategies. By characterizing failed myelin repair
in MS brains, the studies outlined in this proposal should identify novel targets that will enhance repair of the
MS brain.

## Key facts

- **NIH application ID:** 9870955
- **Project number:** 5R01NS096148-05
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Ranjan Dutta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $346,719
- **Award type:** 5
- **Project period:** 2016-05-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870955

## Citation

> US National Institutes of Health, RePORTER application 9870955, MicroRNAs as critical regulators of remyelination in Multiple Sclerosis (5R01NS096148-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9870955. Licensed CC0.

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