The Usher Syndrome (USH) is a clinically and genetically heterogeneous disorder characterized by congenital deafness and retinitis pigmentosa. It is the most common cause of deafness accompanied by blindness. Hair cell replacement or regeneration therapies have not really solved the deafness problem of ear diseases. An alternative to replacing lost hair cells is to prevent their loss in the first place, which is a particularly promising line of investigation. Many USH patients will benefit from cochlear implants, but preservation of spiral ganglion cells is important for success of cochlear implants because a minimal density of spiral ganglion cells is required for effective cochlear implants. Residual hair cells present in the cochlea could promote the survival of spiral ganglion neurons by release of neurotrophic substances. Therefore, discovery of therapeutic targets that prevent hair cell death is the key to helping Usher 1 patients to respond to cochlear implants and other treatment options successfully. Mouse models facilitate experiments to determine the function of the various genes involved in Usher disease. We have developed mouse models for Usher syndrome. Thus, we propose the following specific aims: 1) identify the mutation in and characterize a new mouse deafness model (for Usher 1 syndrome and presbycusis) that provides an ideal window of time for evaluating drug therapy;2) identify key molecules and mechanisms that lead to hair cell death and hearing loss in the models for the Usher 1 syndrome;3) prove the concept that genetic hearing loss and hair cell death can be prevented by otoprotection therapy. Results of the proposed research will benefit human health. Usher Syndrome (USH) accounts for 6% of the congenitally deaf population and more than 50% of the deaf-blind population. Discovery of therapeutic targets that prevent hair cell death is the key to helping Usher 1 patients to respond to cochlear implants and other treatment options successfully. We propose to develop a new mouse deafness model, a model for Usher 1 syndrome and presbycusis, which has an ideal window of time for evaluating drug therapy.

Public Health Relevance

Usher Syndrome (USH) accounts for 6% of the congenitally deaf population and more than 50% of the deaf- blind population. Discovery of therapeutic targets that prevent hair cell death is the key to helping Usher 1 patients to respond to cochlear implants and other treatment options successfully. We propose to develop a new mouse deafness model, a model for Usher 1 syndrome and presbycusis, which has an ideal window of time for evaluating drug therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC009246-01A2
Application #
7653564
Study Section
Auditory System Study Section (AUD)
Program Officer
Watson, Bracie
Project Start
2009-04-01
Project End
2014-03-31
Budget Start
2009-04-01
Budget End
2010-03-31
Support Year
1
Fiscal Year
2009
Total Cost
$333,625
Indirect Cost
Name
Case Western Reserve University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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