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Mol Ther. 2017 Mar 1;25(3):780-791. doi: 10.1016/j.ymthe.2017.01.007. Epub 2017 Feb 21.

Gene Therapy Restores Balance and Auditory Functions in a Mouse Model of Usher Syndrome.

Author information

1
Neurotology Program, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, Bethesda, MD 20892, USA.
2
Laboratory of Molecular Genetics, NIDCD, NIH, Bethesda, MD 20892, USA.
3
Mouse Auditory Testing Core Facility, NIDCD, NIH, Bethesda, MD 20892, USA.
4
Department of Special Education and Communication Disorders, University of Nebraska, Lincoln, NE 68583, USA.
5
Molecular Biology and Genetics Section, NIDCD, NIH, Bethesda, MD 20892, USA.
6
Section on Sensory Cell Biology, NIDCD, NIH, Bethesda, MD 20892, USA.
7
Neurotology Program, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, Bethesda, MD 20892, USA; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA. Electronic address: wade.chien@nih.gov.

Abstract

Dizziness and hearing loss are among the most common disabilities. Many forms of hereditary balance and hearing disorders are caused by abnormal development of stereocilia, mechanosensory organelles on the apical surface of hair cells in the inner ear. The deaf whirler mouse, a model of human Usher syndrome (manifested by hearing loss, dizziness, and blindness), has a recessive mutation in the whirlin gene, which renders hair cell stereocilia short and dysfunctional. In this study, wild-type whirlin cDNA was delivered to the inner ears of neonatal whirler mice using adeno-associated virus serotype 2/8 (AAV8-whirlin) by injection into the posterior semicircular canal. Unilateral whirlin gene therapy injection was able to restore balance function as well as improve hearing in whirler mice for at least 4 months. Our data indicate that gene therapy is likely to become a treatment option for hereditary disorders of balance and hearing.

KEYWORDS:

vestibular dysfunction; whirler; whirlin

PMID:
28254438
PMCID:
PMC5363211
DOI:
10.1016/j.ymthe.2017.01.007
[Indexed for MEDLINE]
Free PMC Article

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