Mice are helping to understand and treat a common disease which leaves many children temporarily deaf.
Researchers at MRC Harwell in Oxfordshire working on the EUMODIC project have found that mice lacking particular genes develop the same deafness symptoms as children with glue ear.
This valuable information is now guiding the development of alternatives to surgery, which is currently the only treatment available.
Glue ear is a condition where the middle ear fills with sticky pus instead of air. The build-up of fluid prevents the three tiny lever-like bones that carry sound vibrations from moving freely, so the sound can’t reach the brain, severely affecting hearing. Glue ear is most common in children, and can lead to language and developmental delays.
The EUMODIC project is part of an international mouse gene study which aims to look at how genes are involved in body processes by monitoring changes when they are removed.
Professor Steve Brown, director of the mammalian genetics unit at MRC Harwell said: “We have found several mice, several different lines with different mutations in different genes that are causing glue ear in our mice. Now, that’s not surprising, we wouldn’t expect one gene to be involved rather there would probably be several genes impacting on different processes involved in developing this chronic inflammation in the middle ear.”
The research contradicts previous thinking that glue ear is caused by an infection. The genetically modified mice have been reared in quarantine away from any pathogens and still develop the condition, indicating that there is a genetic cause.
Hearing is tested with high frequency sound from a 'click box'
Glue ear is the most severe form in a spectrum of middle ear disorders called otitis media. The acute form is caused by pathogens and clears within a few weeks, but chronic otitis media seen in glue ear can last for months.
Eight out of ten children will have experienced glue ear at least once before they reach the age of ten. Those whose condition persists or worsens usually need surgery, which involves inserting a tiny tube called a grommet to help clear the ears.
“Mice with glue ear have helped find that actually it is not caused by an ongoing bacterial insult, rather that something has gone wrong with the ability of these mice to resolve the inflammation,” Professor Brown said.
“That’s important for us because the chronic human disease is the same. Although it might start with a bacterial infection, this acute form, it goes on to develop this chronic form, so-called glue ear. Those children with glue ear they don’t have an ongoing bacterial infection in their middle ears.”
Finding the genes which may predispose children to glue ear will help researchers understand how glue ear develops and may lead to new ways to target the molecules involved.
Quarantined mice are deaf, showing it is a result of genes
Researchers have now started trials in the mouse models to test the effectiveness of drug treatments. A drug normally used to treat cancer, known as a VEGF inhibitor, has proven effective in treating the mouse models. The drug tackles a newly identified root cause of deafness - a lack of oxygen. The drug is non-invasive and can be administered directly into the inflamed site.
As well as developing our understanding of otitis media specifically, the mouse models are also useful for understanding the process of infection in general.
“Our models are working in two ways - we are very excited about that. First of all in just understanding the processes of chronic [glue ear] disease but secondly, potentially as an infection model where we can colonise the middle ears of mice with the human pathogens that are involved with otitis media and use those as models to test out new vaccines,” said Professor Brown.
Main picture from Flickr