This is an RNID-FPA Translational Research Grant awarded to Dr Peter Santa Maria at Stanford University in 2021. We are funding this grant in partnership with Fondation Pour l’Audition.
Background
Chronic suppurative otitis media is a recurrent form of middle ear infection that affects up to 330 million people worldwide. Around 60% of people affected develop permanent hearing loss as a result. It is the most common cause of hearing loss in children in low- and middle-income countries and leads to problems with language and cognitive development.
These ear infections are caused by unwanted bacteria that form communities inside the ear called biofilms. They are currently treated with antibiotic eardrops, which kill the infection-causing bacteria. However, this treatment often does not fully clear the infection, because the biofilms act as protective shields for a special type of “sleeping” bacteria, called persister cells. These persisters, hidden inside the biofilm, survive the antibiotic treatment and then multiply, leading to a relapse of infection.
As a result, people with this condition face a lifelong struggle with the disease, often including multiple rounds of ineffective ear surgery, and with a high risk of completely losing their hearing. A new treatment that targets the persister bacteria in biofilms could break the cycle of chronic middle ear infection and protect millions of people from hearing loss.
Aim
Professor Santa Maria and his lab have developed a new way to study middle ear infections in mice, that is like the human form of the disease. Using these mice, they can track the infection, and the bacteria/biofilm that cause it, in real time. This means they can test new treatments for middle ear infections, and measure how effective they are in killing persister bacteria.
Recently, the team found a way to ‘supercharge’ the effect of the antibiotic eardrops. First, they created microscopic gold particles coated in molecules that “wake up” persister bacteria and make them more vulnerable to antibiotics. Second, they found that by combining standard antibiotics with these particles, the mixture could kill both normal and persister bacteria, completely clearing the middle ear infections in their mice.
The researchers’ overall aim is to develop a new therapy to permanently clear recurrent middle ear infections. With our funding, they will carry out experiments needed to move this new treatment towards clinical trials in people.
In this project, they will:
- Test that the gold particles and the molecules they carry are chemically stable
- Measure how the particles move inside the ear
- Confirm that the particles are safe to use and do not cause damage to the ear or the body
- Calculate the optimal dose of their new treatment for successfully treating a middle ear infection.
Benefit
There are currently no effective medical treatments for chronic middle ear infections, that affect millions of people around the world and are a leading cause of persistent hearing loss. If successful, this project will help advance the development of the first combined therapy to specifically treat recurrent middle ear infection. By confirming the effectiveness and safety of this new treatment, these results will allow the researchers to attract follow-up funding to move this work closer to clinical testing in people. In the longer term, this treatment could prevent millions of people around the world from losing their hearing.