Action on Hearing Loss has funded research to understand how a new drug could protect hearing when they must take medication that can damage hearing. Ototoxic drugs such as the anti-cancer drug cisplatin and some antibiotics can affect the auditory system causing permanent hearing loss, so it is important to find treatments to protect hearing from the side-effects of these life-saving drugs.
Researchers at the University of Sussex (supported by AoHL) have been working with a team at the University of Washington to study a new drug, ORC-13661, that shows promise as such a treatment.
The researchers at Sussex and Washington carried out an in-depth study of ORC-13661 and its protective effects on hair cells. They tested its ability to protect zebrafish (and mouse) hair cells against a range of different aminoglycoside antibiotics (such as gentamicin and amikacin, two of the more commonly used aminoglycosides) and cisplatin. They showed that it protected the hair cells from damage by all the ototoxic drugs it was tested against.
Researchers went on to test whether this was the case in rats treated with the aminoglycoside amikacin. Some of the rats were also given ORC-16331 in their food. The rats treated with ORC-16331 and amikacin didn’t lose their hearing, whereas rats treated only with amikacin did. This suggests that ORC-13661 can get to where it’s needed in the body and protect hair cells from damage caused by aminoglycoside antibiotics.
We know that aminoglycosides damage hair cells because they get into the cells through a special protein channel in the hair cell surface. This channel also happens to be how potassium enters the hair cell in response to sound to trigger a signal to the brain, so it’s quite important for our hearing! The problem is, once the antibiotic gets into the hair cell, it can’t get out. As a result, levels of the antibiotic in the hair cell build up. When those levels get too high, they become toxic and damage (and often kill) the hair cell.
The researchers investigated whether ORC-13661 might interfere with this process. They showed that ORC-13661 reversibly (that is, non-permanently) blocks the protein channel on hair cells. By doing this, it stops the aminoglycoside from getting into the hair cells and damaging them. More importantly, despite temporarily blocking the protein channel that’s crucial for allowing us to hear, it didn’t affect the hearing of rats treated with ORC-13661.
The next stage of its development is for it to be tested in clinical trials in people – and that process has already begun; ORC-13661 is currently being tested in a Phase I trial (the first of three stages of clinical testing). Although there’s still a long way to go before it can be approved for use to protect people’s hearing, AoHL are hopeful that it will be successful. You can read more detail on this study in Tracey Pollard’s blog on the Action on Hearing Loss website.