# Targeting multiple signaling pathways for tinnitus prevention and treatment

> **NIH NIH R44** · GATEWAY BIOTECHNOLOGY, INC. · 2021 · $1,207,345

## Abstract

Subjective tinnitus is the perception of a phantom sound, which negatively impacts the
quality of life for millions of people worldwide. Despite the great demand for remedy, there
are no FDA-approved drugs to prevent or treat tinnitus. Possible causes of tinnitus are
complicated. The current view is that hyperactivity in the central auditory nervous system
contributes to the majority of tinnitus cases. This abnormal electrical activity, including an
increase in delta-band activity, may be the direct result of an increase in T-type calcium
channel activity. Other studies suggest that inflammatory responses within the brain may
be involved in the development and persistence of tinnitus; therefore, drug candidates
targeting both inflammatory and calcium signaling pathways may act synergistically to
prevent and treat tinnitus. Tetrandrine (TET), an approved drug used in China, exhibits
both anti-inflammatory and calcium channel-blocking properties. Using a new tinnitus
detection method in mice, we have shown that both salicylate-induced and noise-induced
tinnitus can be effectively treated by TET in a dose-dependent manner. Our hypothesis
is that TET or its chemical analogs can be developed as drugs to prevent and treat
tinnitus. In our proposed experiments, we have two parallel goals: (1) obtain
investigational new drug (IND)-enabling toxicity and pharmacokinetics data for TET (Aim
1) and (2) optimize second-generation products with structure-activity relationship studies
of TET and its chemical analogs (Aim 2). Successful accomplishment of Aim 1 will enable
TET to advance into clinical development. In addition, the studies of Aim 2 will enable us
to identify additional candidates in case TET fails at clinical stages. By targeting multiple
cellular signaling pathways that impinge upon tinnitus, our study will open new areas for
the treatment and prevention of tinnitus. The extensive body of data publicly available for
TET and its analogs will help us significantly reduce development time and costs.

## Key facts

- **NIH application ID:** 10197878
- **Project number:** 5R44DC018759-02
- **Recipient organization:** GATEWAY BIOTECHNOLOGY, INC.
- **Principal Investigator:** Jianxin Bao
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,207,345
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197878

## Citation

> US National Institutes of Health, RePORTER application 10197878, Targeting multiple signaling pathways for tinnitus prevention and treatment (5R44DC018759-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10197878. Licensed CC0.

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