# Developing a clinical diagnostic tool for age-related cochlear synaptopathy.

> **NIH NIH R42** · GATEWAY BIOTECHNOLOGY, INC. · 2024 · $482,587

## Abstract

Project Summary
Age-related hearing loss (ARHL) is the predominant neurodegenerative disease of aging. Recent
animal studies have demonstrated that the earliest cochlear pathology due to noise and aging
involves a loss of the inner hair cell ribbon synapse. The early consequences of this synaptic loss
are not believed to affect hearing sensitivity, but rather, impair speech understanding in
background noise. While this condition, called cochlear synaptopathy or hidden hearing loss, can
be detected in animal models by a reduction of suprathreshold sound evoked wave-1 amplitude of
auditory brainstem response (ABR) and confirmed by post-mortem quantitative histology, its
diagnosis in humans remains challenging. Several non-invasive electrophysiological methods such
as ABR and electrocochleography (ECochG) have been tested to detect human cochlear
synaptopathy. Two major obstacles to their proposed application include: (1) a high variability of
ABR/ECochG wave amplitudes, and (2) a lack of direct histological validation for living humans.
My strategy here is to develop a new electrical device able to generate calibration pulse to reduce
high variability in ABR/ECochG wave metrics. The validation issue will be addressed by applying
machine learning to identify multiple ABR/ECochG markers associated with cochlear
synaptopathy first in animal models, in which cochlear synaptopathy can be directly validated by
histologic synaptic counting, and then apply these identified features for human diagnosis. My
hypothesis is that clinical diagnosis of human cochlear synaptopathy can be achieved by improving
both hardware and software related for ABR/ECochG data collection and analysis. Based on our
preliminary studies, we will continue to improve our electrical circuit to test if our calibration pulse
device can address the variability issue, and at the same time, we will identify ABR/ECochG
features associated with age-related cochlear synaptopathy in mice and then validate these
identified features in gerbils since its hearing range is similar to humans. Finally, I will perform a
longitudinal study to test identified features in humans during aging.
 Early detection of cochlear synaptopathy may lead to effective preventive strategies that
would delay or potentially prevent further development of ARHL. Completion of this project is
therefore expected to lead to a major shift in current clinical diagnosis of ARHL, while providing
a unique training opportunity for the principal investigator to develop skills in developing
commercial medical devices.

## Key facts

- **NIH application ID:** 10929509
- **Project number:** 5R42AG078721-03
- **Recipient organization:** GATEWAY BIOTECHNOLOGY, INC.
- **Principal Investigator:** Joseph Pinkl
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $482,587
- **Award type:** 5
- **Project period:** 2022-09-30 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929509

## Citation

> US National Institutes of Health, RePORTER application 10929509, Developing a clinical diagnostic tool for age-related cochlear synaptopathy. (5R42AG078721-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10929509. Licensed CC0.

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