Area:
auditory neuroscience, otolaryngology
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High-probability grants
According to our matching algorithm, Lawrence Lustig is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2012 — 2013 |
Lustig, Lawrence R |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Virally Mediated Gene Therapy For Genetic Hearing Loss @ University of California, San Francisco
DESCRIPTION (provided by applicant): Approximately 1.5 in 1000 children are affected by deafness at birth, 1/2 of which can be attributed to a genetic cause. Treatment for these inherited forms of deafness is quite limited, and consists of hearing amplification for mild to severe hearing loss, and cochlear implantation for severe to profound hearing loss. Gene therapy has been suggested as a potential treatment for genetic hearing loss, but success in this area has remained elusive. Important advances have been made towards hair cell regeneration using virally-mediated gene delivery; however breakthroughs in cellular regeneration likely would not benefit those with genetic deafness because the underlying genetic background would be unchanged. Yet the inner ear remains an attractive target for gene therapy due to advances in surgical access and confinement of fluid space by the bony structure of the cochlea. We have been studying a transgenic mouse that is profoundly deaf after deletion of the vesicular glutamate transporter-3 (VGLUT3) gene, the same gene responsible for the human non-syndromic deafness DFNA25. Our recent work has led to successful restoration of hearing in postnatal mice by local monogenic therapy using an adeno- associated viral vector (AAV-VGLUT3). This novel initial finding provides a powerful incentive to investigation if this therapy can be optimized and generalized to other forms of genetic deafness. The overall goals of this proposal are to optimize the viral-gene delivery method to the cochlea for hearing restoration in the VGLUT3 knockout (KO) mouse, verify that normal synaptic physiology is restored, and determine whether this technique can be generalized to another mouse model of genetic deafness, the otoferlin knockout mouse, a model for the human genetic deafness DFNB9. Results from these studies may provide the foundation for future clinical trials in humans with some forms of genetic deafness. PUBLIC HEALTH RELEVANCE: Genetic deafness is a common disorder with limited available treatment options. This research proposal seeks to develop methods of treatment using gene therapy that can be applied to a broad range of genetic hearing losses. If successful, this has the potential to fundamentally change the manner in which genetic deafness is treated
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0.958 |