Mechanisms involved in noise-induced hearing loss include the production of reactive oxygen species and inflammatory cytokines, and stress-related activation of the MAPK/JNK signaling cascade. Each of these responses is connected to the Toll-like receptor signaling cascade. P13 is a potent inhibitor of TLR signaling and we hypothesize P13 will prevent or limit activation of the interconnected signaling pathways that trigger the death of chochlear hair cells, leading to noise-induced hearing loss. Preclinical studies have confirmed the efficacy of P13 both as a preventative and treatment of noise-induced hearing loss.
Noise-Induced Hearing Loss (NIHL) is a significant medical problem. Noise insults leading to hearing loss include work-place associated noises such as machinery, and in the military population, exposure to noises resulting from explosions, blasts, or gunshots, represents an additional risk for hearing loss. Noise-induced hearing loss is the second most common form of sensorineural hearing deficit, after age-related hearing loss. In the US, an estimated 12.5% of children and adolescents aged 6-19 years (approximately 5.2 million) and 17% of adults aged 20-69 (approximately 26 million) have suffered permanent damage to their hearing from excessive exposure to noise and 250 million people workdwide have a NIHL greater than 25 dB, a clinically significant hearing loss. The National Institue of Occupational Safety and Health estimates that approximately 30 million people in the US are exposed hazardous noise, with an economic impact estimated at $242.4 million per year in disability. There are psychological, as well as physiologic effects of noise exposure which may manifest as increased physiologic stress response, adverse social consequences, sleep disturbance, and detrimental economic effects. Currently there is no treatment for noise-induced hearing loss, and prevention is focused on reducing exposure and utilizing hearing protection devices.