title: Gene Therapy Restores Balance and Auditory Functions in a Mouse Model of Usher Syndrome.
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.
authors.affiliation: Neurotology Program, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, Bethesda, MD 20892, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Isgrig
authors.affiliation: Neurotology Program, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, Bethesda, MD 20892, USA.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Shteamer
authors.affiliation: Laboratory of Molecular Genetics, NIDCD, NIH, Bethesda, MD 20892, USA.
authors.forename: Inna A
authors.initials: IA
authors.lastname: Belyantseva
authors.affiliation: Laboratory of Molecular Genetics, NIDCD, NIH, Bethesda, MD 20892, USA.
authors.forename: Meghan C
authors.initials: MC
authors.lastname: Drummond
authors.affiliation: Mouse Auditory Testing Core Facility, NIDCD, NIH, Bethesda, MD 20892, USA.
authors.forename: Tracy S
authors.initials: TS
authors.lastname: Fitzgerald
authors.affiliation: Department of Special Education and Communication Disorders, University of Nebraska, Lincoln, NE 68583, USA.
authors.forename: Sarath
authors.initials: S
authors.lastname: Vijayakumar
authors.affiliation: Department of Special Education and Communication Disorders, University of Nebraska, Lincoln, NE 68583, USA.
authors.forename: Sherri M
authors.initials: SM
authors.lastname: Jones
authors.affiliation: Molecular Biology and Genetics Section, NIDCD, NIH, Bethesda, MD 20892, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
authors.affiliation: Laboratory of Molecular Genetics, NIDCD, NIH, Bethesda, MD 20892, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
authors.affiliation: Section on Sensory Cell Biology, NIDCD, NIH, Bethesda, MD 20892, USA.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Cunningham
authors.affiliation: 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.
authors.forename: Wade W
authors.initials: WW
authors.lastname: Chien
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D015870:Gene Expression; D015316:Genetic Therapy; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism / Q000648:ultrastructure; D006309:Hearing / Q000235:genetics*; D006320:Hearing Tests; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D004856:Postural Balance / Q000235:genetics*; D059547:Stereocilia / Q000378:metabolism / Q000648:ultrastructure; D052245:Usher Syndromes / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy
chemical_list: D008565:Membrane Proteins; C477218:Whrn protein, mouse
keywords: vestibular dysfunction; whirler; whirlin