# Xenon gas treatment to modulate microglia in neurodegenerative diseases

> **NIH NIH R41** · GENERAL BIOPHYSICS, LLC · 2021 · $499,546

## Abstract

PHASE I APPLICATION
 (STTR Program PAS-19-317)
 “Xenon gas treatment to modulate microglia in neurodegenerative diseases”
ABSTRACT
 Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder. Emerging evidence shows
that homeostatic dysregulation of the brain immune system, especially that orchestrated by microglia, plays a
significant role in the onset and progression of the disease. The microglial function is maintained in healthy brain
and is pathogenically dysregulated in AD brain. The prominent genetic risk factors, APOE, is involved in
microglial function. We have recently identified a unique molecular signature for homeostatic microglia and have
developed robust tools to investigate microglial biology in health and disease. We also identified a role for the
APOE-signaling in the regulation of a new microglial subset associated with neurodegeneration and in microglia
surrounding neuritic Ab-plaques in human AD brain, which we have termed MGnD. The major question relates
to microglia-based approach to treat AD is how to modulate microglia phenotype and function. Preservation of
neuronal cells from Aβ induced apoptosis as well as restoration of resident microglial homeostatic function is
critical for the restoration of brain function.
 The goal of this proposal is to validate the Xenon (Xe) gas ability to modulate microglia in AD mouse
model and human, that will lead to development of novel AD treatment. Xe is currently used in human patients
as an anesthetic and as a neuroprotectant in treatment of brain injuries. Xe penetrates blood brain barrier, which
can make it effective therapeutic. Our preliminary data demonstrated in acute and AD mouse models that Xe
delivered through inhalation modulates brain microglia and preserve it in the hemostatic form. In this proposal
we would like to further validate Xe action on microglia in-vivo in AD mice model and in neurogenerative human
microglia. We will address our hypothesis in the following aims:
Aim 1: Investigate whether Xe-gas treatment affects phenotype and function of neurodegenerative
microglia in APP-PS1 mice.
Aim 2: Validate whether Xe-gas treatment affects phenotype and function of neurodegenerative human
microglia.
 Based on results of these work we will be able to develop the inhalation system and protocol for
implementation of the therapeutic method for AD treatment.

## Key facts

- **NIH application ID:** 10259094
- **Project number:** 1R41AG073059-01A1
- **Recipient organization:** GENERAL BIOPHYSICS, LLC
- **Principal Investigator:** Oleg Butovsky
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $499,546
- **Award type:** 1
- **Project period:** 2021-09-30 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10259094

## Citation

> US National Institutes of Health, RePORTER application 10259094, Xenon gas treatment to modulate microglia in neurodegenerative diseases (1R41AG073059-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10259094. Licensed CC0.

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