A translatable form of hypoxia therapy for impaired mitochondrial proteostasis

Ended Project Grant Awarded Last action

Award ID
R56AG088161
Recipient
Awarding agency
Obligated
$472,500

Award facts

Assistance listing
93.866 Aging Research
Completion date
Place of performance
California, USA

Award details come from USAspending.gov.

Description

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.

Transactions

Action Obligated Date
Amendment $0
Original award $472,500

Quick answers

Who received award R56AG088161?

R56AG088161 was awarded to J.david Gladstone Institutes by National Institute on Aging (National Institutes of Health) on September 26, 2024.

How much is award R56AG088161 worth?

$472,500 has been obligated on R56AG088161.

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