This project is funded through our Translational Research Initiative for Hearing (TRIH). It's led by Professor Hrvoje Petkovic at ACIES BIO Ltd in Slovenia. Our TRIH grants fund research projects in the early stages of turning research discoveries into potential new treatments for hearing loss and tinnitus. The project began in March 2014 and will end in June 2017.
Aminoglycoside antibiotics, such as gentamicin and kanamycin, are highly effective in treating a range of bacterial infections. But, alongside this beneficial, and often life-saving, activity, they are also highly toxic to the sensory hair cells in the inner ear. The damage they cause is permanent and leads to hearing loss.
Because of their severe side effects, these antibiotics are now only used in the developed world as a last resort, usually to treat life-threatening infections. But in the developing world they are still widespread, resulting in significant numbers of people in these countries losing their hearing.
Aminoglycoside antibiotic preparations mostly consist of a mixture of related chemicals. Until recently, it was very difficult and expensive to separate out these different chemicals (called congeners) from the complex antibiotic mixture, but technological advances are now making it possible to do so on a large scale – without vastly increasing costs.
Professor Petkovic and his team are using these new techniques to isolate a range of congeners from clinically used antibiotic mixtures, and then testing their antibacterial and ototoxic ('ear-toxic') properties. The researchers hope to identify congeners which are antibacterial without being ototoxic. This could lead to the development of new aminoglycoside antibiotics that do not damage hearing.
Despite their adverse side effects, there are many serious medical conditions where the use of aminoglycoside antibiotics is necessary, such as in treating tuberculosis, lung infections associated with cystic fibrosis and infections in premature babies. In addition, the recent emergence of multi-drug resistant infections has led doctors to increasingly use these antibiotics to treat them and, because they are cheaper, they are the antibiotics of choice in developing countries.
Developing aminoglycosides without ototoxic side effects would prevent permanent hearing loss in patients receiving these life-saving treatments, and allow the expanded use of these antibiotics at a time when new ways to treat multi-drug resistant infections are desperately needed.
Once they've completed this project successfully, Hrvoje and his team hope to attract an industrial partner to support further development of a new aminoglycoside antibiotic.