# Epigenetic Markers and Sustained Cytoprotection for Stroke Treatment

> **NIH NIH R42** · ZYMO RESEARCH CORPORATION · 2022 · $841,419

## Abstract

PROJECT SUMMARY/ABSTRACT
Stroke injury occurs over a long duration through pathologic changes leading to long-term neurologic
dysfunction. There is an urgent need of therapeutic strategies that can provide safe and efficacious therapeutic
effects to the hypoperfused brain with long-lasting endogenous neuroprotection for prevention of long-term
neurologic dysfunction. Sufficient evidence has pointed out that xenon (Xe), a bioactive gas, has profound
neuroprotective effects with advantages of rapid diffusion across the blood-brain barrier (BBB) with minimal side
effects. Researchers at The University of Texas Health Science Center at Houston (UTSCH-H) have been able
to incorporate Xe into liposomes and demonstrated that Xe-liposomal treatment post-stroke resulted in activation
of endogenous brain protection following ischemic stroke. Corroborated mechanisms of Xe cytoprotection
include the activation of endogenous cytoprotective molecules. In a NIH Phase I STTR, UTHSC-H collaborated
with Zymo Research Corporation (Zymo), an experienced epigenetics company. We have shown proof of
concept that intermittent Xenon(Xe)-liposomal treatment after stroke extends endogenous neuroprotection and
induces epigenetic changes. Such sustained endogenous neuroprotection can be distinguished by a panel of
differentially methylated biomarkers indicative of activation of specific signal transduction pathways. As brain
pathological changes/progression post stroke last for months, to be clinically useful, to extend the window for
neuroprotection duration. We hypothesize that endogenous neuroprotection seen via epigenetic markers can be
enhanced and consolidated and into the chronic recovery phase, meanwhile, translate to clinical relevant model.
We do this with a three-phase Xenon administration strategy. Two Xe formulations, Xe- liposomes and oral Xe
formulation, will be used to extend the treatment window. We will establish maximal therapeutic efficacy and
then translate into aged rat to increase rigor. The epigenetic biomarker panel identified in the Phase I STTR will
be used to assess and validate Xe long term neuroprotective effects via the 3-phased administration regime in
our Phase 2 STTR. Our goal is to optimize, validate, and translate the Xe liposomal formulation from phase I
and evaluate a new complementary Xenon cyclodextrin (Xe-CD) formulation for oral administration for the
chronic stroke recovery phase, whilst commercializing both Xe intravenous and oral formulations. We will
continue epigenetic biomarker development as a diagnostic tool for evaluating stroke progression and treatment
effects.
Our aims are: 1) to develop final formulations of Xe-liposomes and Xe-enriched solution, and to evaluate
parameters for product reproducibility and analysis pharmacokinetics of both formulations; 2) to maintain
neuroprotection over a longer duration by adding an oral Xe-CD formulation following the IV acute Xe-liposomal
agent administration (Acute to Chronic Recover...

## Key facts

- **NIH application ID:** 10322190
- **Project number:** 5R42NS098918-03
- **Recipient organization:** ZYMO RESEARCH CORPORATION
- **Principal Investigator:** Keith Booher
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $841,419
- **Award type:** 5
- **Project period:** 2017-05-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322190

## Citation

> US National Institutes of Health, RePORTER application 10322190, Epigenetic Markers and Sustained Cytoprotection for Stroke Treatment (5R42NS098918-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10322190. Licensed CC0.

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