# Xenon gas treatment to modulate microglia in neurodegenerative diseases

> **NIH NIH R41** · GENERAL BIOPHYSICS, LLC · 2022 · $313,552

## Abstract

Administrative Supplement Application PA-20-272
Xenon gas treatment to modulate microglia in neurodegenerative diseases (R41AG073059)
ABSTRACT
ABSTRACT FROM ORIGINAL APPLICATION
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 Aβ-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.
The goal of the original proposal was to investigate the Xenon (Xe) gas treatment to modulate microglia in AD
mouse models and human iPSCs-derived microglia transplanted in humanized AD mice. 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 original specific aims were as follow:
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.
SUPPLEMENTAL APPLICATION INFORMATION:
To make competitive Phase II application and transition to clinical trial, we are planning to hold a pre-IND meeting
with FDA. Developing such pre-IND meeting application was not a part of the original Phase I specific aims, but
is closely connected. This new administrative supplement request will increase the likelihood to achieve
additional critical R&D milestones in the technology development pathway to make us more competitive for
Phase II application and ultimately for raising private-sector capital. The proposed scope of this additional
supplement is within the overall scientific scope of the parent grant, which we will be able to complete by end of
August 2022. The pre-IND submission package should include results of the originally proposed work and should
address the following new specific aims:
Aim 1: Determine PK/PD of Xenon inhalation treatment in an acute model of neurodegeneration and in
APP/PS1 mice. The primary goal of our current efforts is to translate Xenon technology for testing in human AD
patients. To prepare a competitive Phase II application for translation to humans, it is crucial to establish
parameters of dosing base...

## Key facts

- **NIH application ID:** 10617078
- **Project number:** 3R41AG073059-01A1S1
- **Recipient organization:** GENERAL BIOPHYSICS, LLC
- **Principal Investigator:** Oleg Butovsky
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $313,552
- **Award type:** 3
- **Project period:** 2021-09-30 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10617078

## Citation

> US National Institutes of Health, RePORTER application 10617078, Xenon gas treatment to modulate microglia in neurodegenerative diseases (3R41AG073059-01A1S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10617078. Licensed CC0.

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