# Functional Screening of GPCR Small Molecule Libraries for Remyelination Therapies

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

## Abstract

SUMMARY
Damage to myelin from diseases such as multiple sclerosis (MS) results in the disruption of the nerve signal,
damage to the axon, and finally degeneration. To date, there are no therapies for repair or remyelination in MS
and this fact alone illustrates the greatest hope and unmet need for MS patients. Functional screening for small
molecules or biologicals that promote remyelination represents a major hurdle to the identification and
development of rational therapeutics for MS. Recently we implemented a novel functional screen using
fabricated micropillar arrays to identify anti-muscarinic compounds that greatly enhance oligodendrocyte
remyelination (Mei et al., 2014). As many of the promising compounds identified in our initial screen
activated or antagonized G-protein coupled receptor (GPCR) targets, in this proposal, we focus
screening efforts on GPCR small molecule libraries to identify/confirm/validate receptor targets that
either inhibit or promote myelination. We believe that GPCRs represent targetable receptors and
pathways for the development of small molecule therapeutics for MS. In this proposal we will: 1. Perform
high-throughput screening of GPCR small molecule libraries to identify agonists and antagonists that promote
myelination. 2. Identify, confirm and validate novel receptors and pathways responsible for the regulation of
oligodendrocyte differentiation and myelination. 3. Investigate the therapeutic implications of activating or
blocking specific receptors during development and after demyelination. Overall, we believe that our proposal
will not only impart a valuable technical approach but more importantly our data identifies two specific GPCRs,
the muscarinic receptor 1 (M1R) that inhibits (Gq) and the kappa opioid receptor (KOR) that promotes (Gi/Go)
differentiation and myelination of oligodendrocytes both during development and after demyelination.

## Key facts

- **NIH application ID:** 9959511
- **Project number:** 5R01NS095889-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jonah R Chan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $346,719
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959511

## Citation

> US National Institutes of Health, RePORTER application 9959511, Functional Screening of GPCR Small Molecule Libraries for Remyelination Therapies (5R01NS095889-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9959511. Licensed CC0.

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