# Blockade of colony stimulating factor 1 receptor to reduce inflammatory nerve injury

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $429,000

## Abstract

ABSTRACT
With the near-eradication of polio, Guillain-Barré syndrome (GBS) has become the most frequent cause of
acute flaccid paralysis. There are two major forms of GBS, demyelinating and axonal, based on the primary
injury to myelin/Schwann cells or axon of the myelinated nerve fibers, respectively. Current immunomodulatory
treatments are only effective in a proportion of patients. For example IVIG–a first line treatment modality in
GBS–hasten recovery in only ~50% of those treated with this medication. Despite availability of current of
immunotherapies, a significant proportion of patients are left with severe and permanent neurologic sequelae,
including inability to walk independently. There is a dire need for newer/additional immune treatments that can
target relevant pathophysiologic mechanisms and limit the neural injury in acute phase of the disease. Cellular
inflammatory effectors are invoked to play major role in the pathogenesis of demyelinating GBS, whereas
autoantibodies against gangliosides/glycolipids are involved in the pathogenesis of axonal GBS. Human
pathologic studies and data from animal modelling indicate that macrophage lineage cells are final executioner
of nerve injury in demyelinating and axonal GBS. Colony stimulating factor 1 receptor (CSF1R) plays critical
role in proliferation, survival and function of monocytes and fully differentiated macrophages including
transmigration in response to its ligand(s). We hypothesize that blockade of this receptor on macrophage
lineage cells can alter the proinflammatory state of these cells and reduce inflammatory nerve injury. This
hypothesis will be tested by the following specific aims: Aim 1 will examine the efficacy of CSF1R blockade
(with a neutralizing antibody and small molecule inhibitor) in anti-ganglioside antibody-mediated model of
axonal GBS. Aim 2 will examine the efficacy of CSF1R blockade (with a neutralizing antibody and small
molecule inhibitor) in a T-lymphocyte orchestrated animal model of inflammatory demyelinating neuropathy.
CSF1R blocking stratgies in this project are translatable as the small molecuel inhibitor proposed for these
studies is already in a clinical trial and a number of monoclonal CSF1R neutralizing antibodies are in clinincal
development for cancer. This project may help in developing a new treatment strategy that has relevance not
only to GBS but other immune neuropathies including CIDP.

## Key facts

- **NIH application ID:** 10195632
- **Project number:** 1R21NS121621-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** KAZIM A SHEIKH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $429,000
- **Award type:** 1
- **Project period:** 2021-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10195632

## Citation

> US National Institutes of Health, RePORTER application 10195632, Blockade of colony stimulating factor 1 receptor to reduce inflammatory nerve injury (1R21NS121621-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10195632. Licensed CC0.

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