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Developing a drug to protect hearing from ototoxic antibiotics

This is a three-year project led by Dr Allison Coffin, Dr Leen Kawas, Dr Joseph Harding and Dr Peter Steyger at Washington State University, USA. It began in March 2015 and will end in February 2018.

The sound-sensing hair cells in the inner ear can be damaged by particular drugs, such as aminoglycoside antibiotics. These drugs save lives but they cause hearing loss in around one-fifth of people given them.

They are known as ‘broad spectrum’ antibiotics, as they are effective against a wide range of bacterial infections – their use is restricted in the UK, where they are mostly used to protect premature babies from infection, to treat lung infections in people with cystic fibrosis, and to treat tuberculosis. They are used far more widely in developing countries, as they are cheap and because they are effective against tuberculosis, which is still a major problem there.

There are currently no approved therapies that can protect hearing from these ototoxic (ear-toxic) medications. Allison Coffin and her colleagues have developed a new drug, Dihexa, which can be taken orally and does not appear to cause serious side-effects. Preliminary research shows that Dihexa can prevent hair cell loss caused by aminoglycosides.

Project aims

Allison’s team are testing the new drug’s ability to prevent hair cell loss and deafness after treatment with aminoglycosides in zebrafish. Zebrafish are an ideal ‘model’ for testing hearing-related drugs like this because they have hair cells – on the outside of their bodies – similar to the hair cells in our inner ears. They are using zebrafish to work out the most effective dose of Dihexa that can protect hair cells from damage, and will determine how Dihexa acts to protect hair cells. Finally, they will apply this knowledge in mice to determine if Dihexa can prevent drug-induced hearing loss in mammals.

“This work could lead to the development of a drug – that can be given at the same time as life-saving medicines which cause hearing loss – to protect the ear from damage.”

Project benefit

Allison and her team have a clear long-term goal. They want to develop Dihexa as a drug that doctors can give patients along with life-saving ototoxic medications, to prevent hearing loss. Our funding will enable them to prove whether Dihexa can protect hair cells from ototoxic drugs, and if so, how. Once we have this information, Dihexa will move one step closer towards clinical trials in people.