This is a three-year project funded through our Translational Research Initiative for Hearing (TRIH). It is being led by Sylvain Celanire, from Pragma Therapeutics (based in France), in collaboration with Professor Robert Frisina, at the University of South Florida in the USA. They are developing new drugs to treat age-related and noise-induced hearing loss. The project began in March 2016 and will end in February 2019.
Our TRIH grant funds research projects in the early stages of turning discoveries into potential new treatments for hearing loss and tinnitus.
Glutamate is a chemical (also known as a neurotransmitter) that carries signals from the sound-sensing hair cells in the ear to the auditory nerve, which then carries them on into the brain. mGlu7, a protein receptor that detects glutamate, is found on hair cells and auditory nerve cells. When glutamate binds to mGlu7, the auditory nerve is activated.
When hair cells become damaged by noise or ageing, they release an excess of glutamate that over-stimulates the auditory nerves nearby, causing them to die and resulting in hearing loss. Genetic studies in people have shown that changes in the mGlu7 gene are associated with susceptibility to age-related and noise-induced hearing loss, suggesting that normalising the function of mGlu7 could help to prevent or treat hearing loss.
In this project, researchers will develop groups of new drugs that will either turn up or turn down the activity of the mGlu7 receptor. The researchers will test if altering mGlu7 function with these drugs is able to restore hearing in animal models of age-related hearing loss and noise-induced hearing loss.
The researchers will synthesise groups of drug-like compounds that will either turn up or turn down the activity of the mGlu7 receptor, and will test the effects of these compounds in animal models of age-related, and noise-induced hearing loss. The best compounds will be further developed so that they can be delivered orally (taken as a tablet). The effect of the new drugs on hair cells, auditory nerves and auditory signalling to the brain will be studied in detail using a range of biological techniques.
Hearing loss affects one in six of the UK population, but there are no medicines approved to prevent or treat hearing loss. This project aims to address this by identifying new drug-like compounds that can alter the function of the mGlu7 receptor, and establish if these compounds have a beneficial effect in treating age-related, and noise-induced, hearing loss. It is a new approach, which, if successful, will identify potential new medicines.
The researchers will develop compounds that reach the ear from the bloodstream, meaning that the drug could be taken as a tablet rather than having to be injected through the eardrum. It will also open up a new area of research for treatments that target glutamate in the auditory system.
The project team brings together the therapeutic drug discovery expertise of Pragma Therapeutics (a small start-up company) with the in-depth hearing research expertise of Professor Frisina’s team at the University of South Florida at Tampa.