Gene therapy restores hair cell stereocilia morphology in inner ears of deaf whirler mice

Wade W. Chien, Kevin Isgrig, Soumen Roy, Inna A. Belyantseva, Meghan C. Drummond, Lindsey A. May, Tracy S. Fitzgerald, Thomas B. Friedman, Lisa L. Cunningham

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)17-25
Number of pages9
JournalMolecular Therapy
Volume24
Issue number1
DOIs
StatePublished - Feb 1 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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