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Finding drugs that affect hair cell regeneration

Dr Ed Rubel at the University of Washington.'Provide a new list of drugs that will facilitate efforts to restore hearing.'

This was three year project at Virginia Merrill Bloedel Hearing Research Centre and run by Prof Edwin Rubel, Dr Jennifer Stone and Dr David Raible. It is was completed in September 2010.

Background

A common reason for hearing loss is damage to the delicate sensory hair cells in our inner ear. Once these are damaged or lost in mammals, the resulting hearing loss is permanent. However, other animals, such as birds, are able to re-grow the sensory hair cells in their ear and thus repair their hearing after damage. To develop therapies to re-grow the lost hair cells in humans, we first need to understand how other animals manage to re-grow their hair cells.

Fish have hair cells along the length of their body. These are used to sense whether they are swimming with or against the current. When damaged, these hair cells re-grow within 72 hours. Because the fish's hair cells are along the outside of their bodies, these can easily be seen and allow scientists to study how they re-grow, giving us important clues about future human treatment.

Aim

In this study, a team of scientists around Prof Ed Rubel investigated the effects that drugs and drug-like compounds have on hair cell regeneration in zebrafish.

Impact

  • Investigating which drugs influence the fish's ability to re-grow their hair cells will help us to find drugs to encourage human hair cells to re-grow and restore hearing. 
  • Screening drugs for effects on hair cells will also allow us to identify drugs which could cause damage to hair cells, and thus hearing loss, as a side effect.

Findings

The team has now tested the effect of 1680 FDA-approved drugs on hair cell regeneration in zebrafish. They have found six drugs that consistently prevent or reduce hair cell regeneration (inhibitors). They have found two drugs that consistently increase or enhance hair cell regeneration (enhancers).

There could be different mechanisms leading to the prevention or enhancement:

  1. inhibition/enhancement of creation of new cells 
  2. inhibition/enhancement of the process to turn cells into hair cells 
  3. cause/prevention of further hair cell death after regeneration.

Current evidence suggests that the two strongest inhibitors prevent the creation of new cells (mechanism 1) while the mechanism of the other four inhibitors has not yet been identified. The two enhancers appear to increase the creation of new cells (mechanism 1) and lead to increased regeneration of hair cells.

Next steps

The study has allowed the scientists to evaluate a large number of drugs and identify which influence hair cell regeneration. They now plan to test the identified drugs in well-established models to further understand how these drugs affect sensory hair cells.

Published: December 2010

Get in touch

Biomedical research - beakers.For further information on this project or our Biomedical Research programme, please contact:

Action on Hearing Loss (the new name for RNID)
19-23 Featherstone Street
London EC1Y 8SL

Telephone: 0808 808 0123
Textphone: 0808 808 9000

Email: research@hearingloss.org.uk

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