title: Gene Therapy Restores Hair Cell Stereocilia Morphology in Inner Ears of Deaf Whirler Mice.
abstract: Hereditary deafness is one of the most common disabilities affecting newborns. Many forms of hereditary deafness are caused by morphological defects of the stereocilia bundles on the apical surfaces of inner ear hair cells, which are responsible for sound detection. We explored the effectiveness of gene therapy in restoring the hair cell stereocilia architecture in the whirlin mouse model of human deafness, which is deaf due to dysmorphic, short stereocilia. Wild-type whirlin cDNA was delivered via adeno-associated virus (AAV8) by injection through the round window of the cochleas in neonatal whirler mice. Subsequently, whirlin expression was detected in infected hair cells (IHCs), and normal stereocilia length and bundle architecture were restored. Whirlin gene therapy also increased inner hair cell survival in the treated ears compared to the contralateral nontreated ears. These results indicate that a form of inherited deafness due to structural defects in cochlear hair cells is amenable to restoration through gene therapy.
authors: Neurotology Program, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health, Bethesda, Maryland, USA.|Department of Otolaryngology-Head & Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors: Wade W
authors: WW
authors: Chien
authors: Section on Sensory Cell Biology, NIDCD, National Institutes of Health, Bethesda, Maryland, USA.
authors: Kevin
authors: K
authors: Isgrig
authors: Section on Sensory Cell Biology, NIDCD, National Institutes of Health, Bethesda, Maryland, USA.
authors: Soumen
authors: S
authors: Roy
authors: Laboratory of Molecular Genetics, NIDCD, National Institutes of Health, Bethesda, Maryland, USA.
authors: Inna A
authors: IA
authors: Belyantseva
authors: Laboratory of Molecular Genetics, NIDCD, National Institutes of Health, Bethesda, Maryland, USA.
authors: Meghan C
authors: MC
authors: Drummond
authors: Section on Sensory Cell Biology, NIDCD, National Institutes of Health, Bethesda, Maryland, USA.
authors: Lindsey A
authors: LA
authors: May
authors: Mouse Auditory Testing Core Facility, NIDCD, Bethesda, Maryland, USA.
authors: Tracy S
authors: TS
authors: Fitzgerald
authors: Laboratory of Molecular Genetics, NIDCD, National Institutes of Health, Bethesda, Maryland, USA.
authors: Thomas B
authors: TB
authors: Friedman
authors: Section on Sensory Cell Biology, NIDCD, National Institutes of Health, Bethesda, Maryland, USA.
authors: Lisa L
authors: LL
authors: Cunningham
mesh_terms: D000818:Animals; D002470:Cell Survival; D003638:Deafness / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000166:cytology / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D059547:Stereocilia / Q000378:metabolism / Q000648:ultrastructure*; D016896:Treatment Outcome
chemical_list: D008565:Membrane Proteins; C477218:Whrn protein, mouse