Article
Regeneration of vestibular hair cells and functional rehabilitation by gene therapy with Math1 in the mouse
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Authors
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Mark Praetorius
- University Hospital Heidelberg, Dept. of Otolaryngology, Head and Neck Surgery, Heidelberg
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Hinrich Staecker
- University of Maryland, Department of Otolaryngology, Head and Neck Surgery, Baltimore, MD, USA
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Douglas Brough
- Genvec, Inc., Gaithersburg, MD, USA
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Kim Baker
- University of Maryland, Department of Otolaryngology, Head and Neck Surgery, Baltimore, MD, USA
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Peter K. Plinkert
- University Hospital Heidelberg, Dept. of Otolaryngology, Head and Neck Surgery, Heidelberg
| Published: | September 22, 2005 |
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Outline
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Introduction: Vestibular dysfunction is a common and for the affected severe disease. In neonatal cell culture models of organs of Corti or revealed an inducement of the generation of hair cells due to an overexpression of Math1. This establishment of hair cells as an effect of math1 had been observed also in vivo.
Methods: We have investigated an organotypic cell culture, and unilateral acute and bilateral chronic model of the mouse for damage with amino glycosides. Transfection with Math1 was performed with an adenoviral vector (AdMath1.11D)
Results: Following overexpression of Math1, new hair cells were seen in cultures of utricles and sacculae of adult mice. In mice treated acutely or chronically with amino glycosides, after treatment with AdMath1.11D into the inner ear, the neuroepithelium of the vestibular organ showed clear signs of restitution. Interestingly, in the cochleae of these mice, no new hair cells were seen, such as outside the vestibular neuroepithelium. Examination of mice treated with amino glycosides and AdMath1.11D two months after gene therapy showed robust improvement of times in the swim test compared to mice treated with amino glycosides alone.
Conclusions: We could show in this study that in vivo generation of new vestibular hair cells under the influence of Math1 is also possible in adult mice. Beyond the morphologic changes, for the first time an objective functional improvement in the animal model is feasible.
