Repair of the vestibular system via adenovector delivery of Atoh1: a potential treatment for balance disorders.
Loss of auditory and vestibular hair cells is a common cause of hearing loss and balance disorders. A variety of strategies have been proposed to restore function to damaged inner ear neuroepithelium. Delivery of the atonal homolog, atoh1, has been demonstrated to induce recovery of auditory and vestibular hair cells using a variety of delivery methods and model systems. We have developed a mouse model of vestibular aminoglycoside ototoxicity and demonstrated that delivery of an advanced generation adenovector that expresses atoh1 results in the regeneration of vestibular hair cells. Additionally, mice treated with atoh1 recover balance function. Currently vestibular diseases have few treatment options and several lines of evidence suggest that regeneration of hair cells may be more easily accomplished in the vestibular system. Development of atoh1-based gene therapy for vestibular hair cell loss may provide an initial opportunity for developing gene therapy for inner ear disease.
Baker
Kim
K
Brough
Douglas E
DE
Staecker
Hinrich
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006198:Hair Cells, Auditory / Q000502:physiology*; D006319:Hearing Loss, Sensorineural / Q000628:therapy; D006801:Humans; D051379:Mice; D009924:Organ Culture Techniques; D004856:Postural Balance; D012678:Sensation Disorders / Q000628:therapy*; D015837:Vestibular Diseases / Q000628:therapy*
D051792:Basic Helix-Loop-Helix Proteins; C500942:ATOH1 protein, human