# The role of Pou4f3 in age-related vestibular dysfunction

> **NIH NIH R01** · UNIVERSITY OF MISSISSIPPI MED CTR · 2022 · $648,413

## Abstract

Project Summary:
It has been estimated that more than 40% of older adults suffer vestibular (i.e. balance) deficits.
These losses cause numerous other problems associated with aging including cognitive decline
and injurious or fatal falls. There is also a strong link between age-related vestibular dysfunction
(ARVD) and Alzheimer's disease and related dementias. Despite the prevalence of these issues
and the massive toll they exert on public health and associated financial costs, the underlying
causes for ARVD are poorly understood. As a result, there are currently no FDA approved
therapies for ARVD. While a deep understanding of mechanistic causes is lacking, it has been
known for some time that a very common pathology that causes age related inner ear
dysfunction is the death of sensory cells called hair cells. Exactly why these cells die with age
remains a mystery. Here, we have identified a previously uncharacterized pattern in the
expression of the pro-survival gene, Pou4f3, where it is normally highly expressed in inner ear
hair cells, but is downregulated with age in a fashion that is correlated with hair cell death in the
balance organs of the inner ear. Furthermore, preliminary data suggest that deleting Pou4f3
causes detrimental phenotypes in vestibular hair cells, exacerbates hair cell death, and leads to
significant declines in vestibular function. We propose to build on these preliminary data by
further examining Pou4f3 changes in expression in vestibular organs with age and in models of
Alzheimer's disease. We will also more thoroughly characterize the effects of Pou4f3 deletion to
better understand the effects that deletion or hypomorhpism have on balance and neurological
functions. We also propose to examine genomic regulatory elements in inner ear tissues from
young and aged mice to identify causal mechanisms for Pou4f3 downregulation with age as well
as possibly discover other key genes involved in aging processes in the inner ear. Finally, we
will test whether overexpression of Pou4f3 can prevent sensory cell death and age related
vestibular declines. Our preliminary data suggest that Pou4f3 is a promising therapeutic target
for preserving balance function in the aging human population. The experiments proposed will
determine the validity of that overarching hypothesis and will provide a foundation from which to
launch several new investigations into Pou4f3-targeted pharmacological and gene therapy
approaches for the prevention of age related vestibular decline.

## Key facts

- **NIH application ID:** 10468947
- **Project number:** 5R01AG073151-02
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR
- **Principal Investigator:** Brandon C. Cox
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $648,413
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468947

## Citation

> US National Institutes of Health, RePORTER application 10468947, The role of Pou4f3 in age-related vestibular dysfunction (5R01AG073151-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10468947. Licensed CC0.

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