In this project, Professor Corné Kros at the University of Sussex investigates possible mechanisms of drug-induced hearing loss by looking at proteins present on the membranes surrounding the sound-sensing cells.
Project start date: September 2021
Project end date: March 2025
Read about the project outcomes here.
About the project
Certain important medicines that are used to treat life-threatening conditions, such as sepsis (blood poisoning) and cancer, can cause hearing loss as a side effect. Among these are a type of antibiotics called aminoglycosides, and an anti-cancer drug called cisplatin.
In this project, researchers seek to deepen our understanding of how aminoglycosides and cisplatin kill the sound-sensing cells of the inner ear, which are called hair cells and are essential for hearing. They aim to use this knowledge to find ways to reduce or prevent hearing loss in people treated with them.
How it works
Previous work by the team found that these drugs impact proteins called VRACs located on the membranes that surround hair cells, but they do so in different ways. The researchers will test how hair cells and their VRACs are affected by both aminoglycosides and cisplatin.
They will also test the hearing of mice which lack a key part of the VRACs, a component that’s specifically needed for cisplatin to enter cells. Cancer cells lacking this part are resistant to cisplatin treatment: the researchers will test whether the hair cells are also protected from damage.
How will this research benefit people at risk of hearing loss?
This research will show how VRACs in hair cells contribute to the ototoxic side effects of aminoglycosides and cisplatin. This will then allow researchers to develop treatments to target VRAC proteins and selectively protect hearing, without affecting the antibiotic or anticancer effects of these medicines.
What we’ve learned so far
The researchers found that, despite lacking the part of the VRAC proteins important for cisplatin to enter the cells, the hair cells could still be damaged by cisplatin. Further research is needed to understand how VRAC proteins contribute to drug-induced hearing loss and could be targeted to prevent it.
About the researcher
Professor Corné Kros is Emeritus Professor at the University of Sussex. He was awarded an RNID Discovery Research Grant for this project in 2021.