# A Translatable Form of Hypoxia Therapy for Impaired Mitochondrial Proteostasis

> **NIH NIH R56** · J. DAVID GLADSTONE INSTITUTES · 2024 · $472,500

## Abstract

PROJECT ABSTRACT
Our previous work demonstrated that hypoxic breathing, simulating high-altitude living, can prevent and reverse 
neurological damage in a mouse model of mitochondrial electron transport chain (ETC) deficiency caused by 
mutations in a key complex 1 subunit. This research revealed that chronic hypoxia significantly extends lifespan 
and rescues biomarkers, behavior, and neuropathology. Building on these findings, a Phase 1 clinical trial 
exposing healthy volunteers to controlled hypoxia was performed.
To expand the understanding of hypoxia therapy's broader applicability, we are now testing the ability of low 
oxygen to rescue additional mitochondrial diseases caused by mutations in the mitochondrial proteostasis 
system. Furthermore, we propose investigating two potential mechanisms of hypoxia-mediated rescue: (1) 
activation of the hypoxia-inducible factor (HIF) transcriptional response to promote metabolic adaptations and 
(2) stabilization of iron-sulfur (Fe-S) cluster-containing protein complexes affected by ETC dysfunction.
By elucidating these mechanisms, this research will provide critical insights into optimizing hypoxia-based 
therapies for mitochondrial diseases and inform treatment strategies for broader clinical applications.

## Key facts

- **NIH application ID:** 11170840
- **Project number:** 1R56AG088161-01
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Isha Himani Jain
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $472,500
- **Award type:** 1
- **Project period:** 2024-09-26 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11170840

## Citation

> US National Institutes of Health, RePORTER application 11170840, A Translatable Form of Hypoxia Therapy for Impaired Mitochondrial Proteostasis (1R56AG088161-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11170840. Licensed CC0.

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