Ammonium tetrathiomolybdate improves auditory and vestibular function after gentamicin exposure via the NRF2-GPX4 axis

Gentamicin-induced inner-ear injury can cause disabling vestibular dysfunction and hearing loss; however, the regulated death programs driving vestibular and cochlear hair-cell loss remain incompletely defined. In this study, we identify ferroptosis as a shared and central mechanism of gentamicin-induced vestibular and cochlear toxicity in mice....

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No actionable change — this is a preclinical animal/molecular study; ammonium tetrathiomolybdate has not been tested in humans for aminoglycoside ototoxicity protection.

Identifying the NRF2-GPX4 pathway as a druggable target for aminoglycoside ototoxicity opens a potential new avenue for pharmacological inner-ear protection, a field with very few approved interventions.

1. 01Ammonium tetrathiomolybdate (ATM) reduced gentamicin-induced hair-cell death in a preclinical model.
2. 02The protective mechanism operates through the NRF2-GPX4 axis, regulating ferroptosis and oxidative stress in cochlear/vestibular hair cells.
3. 03Both auditory and vestibular function improved in gentamicin-exposed animals treated with ATM.
4. 04Study is published in Molecular Therapy, a peer-reviewed journal focused on gene and molecular medicine.
5. 05No human or clinical trial data are yet available for this compound in this indication.

PMID

42687382

DOI

10.1016/j.ymthe.2026.09.002.

Journal

Molecular Therapy

Publication type

research_article

Evidence level

4

Population

Animal/preclinical model of gentamicin-induced inner-ear injury (cochlear and vestibular hair cells)

Intervention

Ammonium tetrathiomolybdate (ATM) administered after gentamicin exposure

Comparator

Gentamicin-exposed controls without ATM treatment