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      Finding potential new drugs to reconnect the inner ear to the brain

      This three-year project is led by Dr Lavinia Sheets at the University of Washington in St Louis, USA. It will end in November 2019.

      Background

      Our inner ears contain exquisitely sensitive sensory receptors, hair cells, that detect sound waves travelling through the air. These hair cells transform sound information into an electrical signal that is sent to the brain via the auditory nerve, allowing us to perceive it. Sensorineural hearing loss – the most common type of hearing loss – is caused by damage to the inner ear, and occurs when hair cells, auditory nerve cells, or the connections between them are lost. This can happen in a number of ways – for example, through exposure to damaging levels of noise or medicines for other conditions, which harm the cells in the inner ear. This hearing loss is permanent, and leads to problems with understanding speech, and listening in noisy environments. 

      The main treatments for hearing loss are hearing aids and cochlear implants. However, these devices can’t work very well when hearing loss is due to loss of or damage to the auditory nerve (without the nerve, neither device can pass sound information to the brain). 

      Project aims

      The aim of this project is to identify biological processes that can promote regeneration of the auditory nerve and re-connection of hair cells to the auditory nerve. The researchers will do this by performing a large-scale screen of FDA-approved drugs and other bioactive molecules (substances which have a biological effect on cells or organisms) in zebrafish. 

      Zebrafish are frequently used to carry out large drug screens of this type – and they are especially valuable for screening drugs that could treat hearing loss, as they have hair cells that are very similar to the ones in our inner ear along the outside of their bodies, which they use to sense movement in the water around them. These hair cells also have nerve connections that are very similar to those in our inner ear. The researchers will use zebrafish to screen around 2,000 compounds with known bioactive properties, measuring how each one affects the regeneration of nerve cells and the connections between them. They hope to find chemicals that can be further developed into treatments for sensorineural hearing loss, or to find new biological processes that are involved in regeneration that could be targeted. 

      Benefit

      There are currently no approved drugs to treat sensorineural hearing loss. Finding drugs that can promote regeneration or repair of the auditory nerve, or drugs which help disconnected hair cells to re-form connections to the auditory nerve, could lead to the development of effective treatments for people whose hearing loss is caused by an absent or damaged auditory nerve by re-establishing signalling between the ear and the brain.

      Zebrafish Regeneration
      Zebrafish regeneration