Novel small molecules for prevention or treatment of hearing loss

A family of quinolyl nitrone derivatives has been identified as potential agents for the prevention or treatment of hearing loss caused by physical factors, such as noise or exposure to ototoxic substances.

Market need: Hearing loss is a significant public health concern due to its high prevalence and profound impact on quality of life. Numerous environmental factors contribute to hearing loss, with noise exposure and ototoxic substances being among the most notable. Many clinically used drugs, including antibiotics, antitumor agents, anti-inflammatory, and antimalarial medications, have ototoxic side effects.
Currently, there is no curative treatment for hearing loss; the only available options are assistive devices such as hearing aids or cochlear implants. This highlights the urgent need for new pharmacological therapies that can effectively prevent or treat hearing loss.

Proposed solution: A protective effect against noise-induced hearing loss has been demonstrated in mice treated with a nitrone compound. The mice were exposed to 105 dB SPL of noise inside a reverberation chamber, and the compound was administered intraperitoneally every 12 hours, beginning before noise exposure and continuing for three days. Nitrone-treated animals exhibited significantly lower auditory thresholds compared to those receiving only the vehicle.
The otoprotective effect was further assessed in cell cultures treated with H₂O₂. Nitrone-treated cells showed increased viability across all tested doses. Unlike the reference antioxidant N-acetyl cysteine (NAC), nitrones provided protection at all H₂O₂ concentrations tested.

Competitive advantages

Lead compounds aren’t toxic and have shown protection against hearing loss in mice exposure to noise and in cell cultures treated with H2O2.
The protective effect provided by quinolyl nitrones in the earliest stages of the lesion together with the absence of toxicity may be of great importance for protection or managing of hearing impairment.