. 2018 Jul 1;7(1):107–115. doi: 10.1089/biores.2018.0017

Table 2.

Selected Key Points

• Roughly 1 in 15 people worldwide—about 500 million—suffer from disabling hearing loss; two to three times that number have mild-to-complete hearing loss.^12,13

• Recent studies proclaim hearing problems as the fourth leading cause of YLDs; clearly a major global health concern.^10–12

• Hearing impairment has been called an “invisible disability” despite its significant consequences, economic and personal; the impact is most substantial in LMICs, where >80% of people with hearing loss reside.⁴⁴

• Noise exposure is a major cause of deafness and hearing impairment (i.e., noise-induced hearing loss); cardiovascular risk caused by diabetes and smoking is also associated with hearing loss.²²

• Hearing impairment in children and adults may also present as sequelae of cytomegalovirus, Ebola virus, and other serious infections.^14,75,77,121

• Advanced age is a major risk factor for hearing loss (i.e., presbycusis, age-related hearing loss), with U.S. prevalence nearly 70% over age 70; indeed, age-related hearing loss may prove to be a useful biomarker and treatable risk factor for cognitive decline or impairment, including Alzheimer's disease.^43–46

• Hearing loss has been observed following TBI, and while it is significant clinically it is yet to be well characterized.^92,136

• Genetics, both mitochondrial and nuclear, and demographics (educational level, race/ethnicity, sex) have an influence on, or are associated with, hearing disorders.^{24,62,63,65,66,72,82}

• The most common congenital sensory impairment is hearing loss, affecting between 1 in 300 to 500 newborns and children to the age of 4; one example results from disruption of a gene that encodes a major component of cochlear gap junctions.¹³⁷

• It is not uncommon to see links between sensorineural deficits in both the ear and the eye; RP, an inherited eye disease, is in some cases associated with reduced hearing ability.^65,66,75,89

• Sensorineural hearing loss is found in mitochondrial respiratory chain disorders, and mtDNA mutations represent one of the most important causes of hearing loss Table 1^{24,62,63,65,66}; given the high energy demands of hearing, mitochondrial involvement should not be a surprise.^60,61

• Certain drugs (Fig. 3), notably aminoglycoside antibiotics (gentamicin), antivirals (ganciclovir), antifungals (amphotericin B), antimalarials (chloroquine), antituberculosis agents (capreomycin), cardiovascular drugs (furosemide), anticonvulsants (valproic acid), cisplatin (platinol), and immunosuppressants (tacrolimus), can result in significant hearing loss.^16,28 Ototoxicity is a potential side effect of some commonly used NSAID and related medications, including acetaminophen (paracetamol) and ibuprofen when taken in very high doses or used chronically (≥2 days/week).⁴² In lieu of a recent study suggesting that, if started early enough, a daily regimen of ibuprofen can prevent the onset of Alzheimer's disease,¹³⁸ ototoxicity in this protocol is an important consideration to take into account.

• From a pharmaceutical perspective, the chemical structural diversity (Fig. 3) of potentially ototoxic drugs is noteworthy.

• Drug discovery to identify novel therapeutics that protect hair cells from toxic insults is experimentally challenging owing to the inaccessibility of the inner ear, but zebrafish and other animal models have been explored; screens have identified multiple potential drug classes of interest, for example, antioxidants,¹²² and other compounds acting on classical GPCR neurotransmitter systems (i.e., adrenergic, dopaminergic, serotoninergic) and estrogen receptor modulators.^{28,29,32,37,57,65,99}

• Biotechnology and pharmaceutical companies have recognized the unmet medical need and therapeutic potential of new drugs for hearing impairment, as exemplified by ventures such as Aurin, Auris, Autifony, Decibel, Frequency, Novus, Otonomy, Sensorion, and Sound, among others^10,13,31,97; still relatively untapped in this respect are epigenetic and mitochondrial targets.^{8,14,18,26,27,30,34,57,82,98,99,132,139–141}

GPCR, G-protein-coupled receptor; LMICs, low- and middle-income countries; NSAID, nonsteroidal anti-inflammatory drug; RP, retinitis pigmentosa; TBI, traumatic brain injury; YLDs, years lived with disability.