HEARING LOSS: WHAT'S IN THE PIPELINE?

摘要

Hearing loss due to aging, hereditary factors, noise exposure, ototoxic drugs and infection is a major healthcare problem. While the causative agents of hearing loss are diverse, many share common sequelae involving oxidative stress, generation of reactive oxygen and nitrogen species, depletion of antioxidant enzymes and signaling pathways leading to apoptosis or necrosis. During the past decades, a host of new strategies for preventing hearing loss have been evaluated. Animal studies have identified a variety of exogenous antioxidants or compounds that enhance antioxidant defenses, providing significant protection. An alternative therapeutic approach involves the use of small molecules to suppress downstream signaling pathways involved in apoptosis. Since many insults lead to inflammation, a third approach has focused on antiinflammatory drugs, some of which suppress the immune system. Finally, growth factors and neurotrophic factors represent a new method to protect and promote the survival of hair cells and neurons in the inner ear. While a great deal is now known about the efficacy of individual compounds, future efforts might benefit from a multifactorial approach involving therapeutic "cocktails" that optimize the degree of protection against age-related hearing loss and other ototraumatic insults.