Reducing the Irreversible Cochlear Toxicity Effects of Aminoglycosides and Antibiotics Required to Treat Diseases

Hearing level accuracy is crucial for our ability to communicate with others. Loss of hearing can lead to reduced ability to communicate with the environment, leading to loss of educational and employment training and opportunities. Aminoglycoside antibiotics have a significant role within the clinically useful antibiotics that are used in order to treat serious infections such as tuberculosis and cystic fibrosis. However, the result of such treatment may lead to hearing loss. This antibacterial drug interferes with the bacterial translation process by binding to the A-site, the bacterial ribosome decoding region and thus, causing protein synthesis disruption. In our study, we are addressing the major toxic mechanism of aminoglycosides through chemical modifications and testing their influence on mammalian hair cells in cochlear organotypic cultures. Once a dose response curve will be made as a function of aminoglycosides concentration, hair cell loss, if any, will be quantified. Aminoglycosides that do not cause harm to hair cells will be injected into mice models, to evaluate their efficacy in vivo. Funded by the Tel Aviv University Breakthrough Innovative Research Grant.