Aminoglycoside antibiotics, such as gentamicin and kanamycin, are a group of powerful antibiotics, effective against a range of bacterial infections. However, they are also toxic to the sound-sensing hair cells of the inner ear (that is, they are ototoxic, oto- meaning ‘ear’). The damage they cause to hair cells is permanent and causes hearing loss, which persists after antibiotic treatment stops.
Despite these toxic side effects, there are serious, life-threatening infections where the use of these antibiotics is necessary, such as for treating tuberculosis, lung infections associated with cystic fibrosis and infections in premature babies. The subsequent hearing loss can have a profound impact, especially in children where hearing loss often occurs before or during the learning of language. In addition, the recent emergence of multi-drug resistant infections has led doctors to increasingly turn to aminoglycoside antibiotics, which are still effective against them. Their low production cost also makes them the antibiotics of choice in low- and middle-income countries, resulting in a considerable burden of hearing loss in these countries.
The aim of this project is to discover medicine-like compounds that can prevent aminoglycosides from causing hearing loss without affecting their ability to treat dangerous infections. The researchers have previously identified over 20 compounds that can protect hair cells from aminoglycoside toxicity in the lab. The team will now test whether these compounds can protect hair cells and hearing in fully mature living animals – an essential step in identifying potential new medicines. They will also check that the compounds do not interfere with the anti-bacterial activity of the antibiotics.
Aminoglycoside antibiotics remain the treatment of choice for many life-threatening infections, but it is estimated that up to half of people treated with them develop some degree of hearing loss. New medicines that can prevent aminoglycoside-induced damage to inner ear hair cells could be given to people during their course of treatment, and preserve their hearing, when they are given these life-saving antibiotics.