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Vestibular Hair Cell Regeneration and Restoration of Balance Function Induced by Math1 Gene Transfer

Staecker, Hinrich*; Praetorius, Mark; Baker, Kim*; Brough, Douglas E.

doi: 10.1097/MAO.0b013e31802b3225
Vestibular Pathology
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Hypothesis: Delivery of math1 using an adenovector (Admath1.11D) results in vestibular hair cell regeneration and recovery of balance function in ototoxin-treated adult mice.

Background: Loss of peripheral vestibular function is associated with disease processes such as vestibular neuronitis, aminoglycoside ototoxicity, and aging. Loss of vestibular hair cells is one of the mechanisms underlying balance dysfunction in all of these disorders. Currently, recovery from these diseases relies on central vestibular compensation rather than on local tissue recovery. Overexpression of the mammalian atonal homologue math1 has been demonstrated to induce generation of hair cells in neonatal organ of Corti cultures and in the guinea pig cochlea in vivo and could thus provide an approach to local tissue recovery.

Methods: Admath1.11D was applied to cultures of aminoglycoside-treated macular organs or in vivo in a mouse aminoglycoside ototoxicity model. Outcome measures included histologic examination, immunohistochemistry, swim testing, and evaluation of the horizontal vestibulo-ocular reflex.

Results: Delivery of math1 resulted in the generation of vestibular hair cells in vitro after aminoglycoside-mediated loss of hair cells. Math1-treated mice showed recovery of the vestibular neuroepithelium within 8 weeks after Admath1.11D treatment. Assessment of animals after vector infusion demonstrated a recovery of vestibular function compared with aminoglycoside-only-treated mice.

Conclusion: Molecular replacement of math1 may provide a therapeutic means of restoring vestibular function related to vestibular hair cell loss.

*Otolaryngology Head and Neck Surgery, University of Kansas School of Medicine, Kansas City, Kansas, U.S.A.; †Department of Otolaryngology, University of Heidelberg, Heidelberg, Germany; and ‡GenVec Inc., Gaithersburg, Maryland, U.S.A.

Address correspondence and reprint requests to Hinrich Staecker, M.D., Ph.D., Department of Otolaryngology Head and Neck Surgery, University of Kansas School of Medicine, 3901 Rainbow Blvd, Mailstop 3010, Kansas City, KS 66160, U.S.A.; E-mail hstaecker@kumc.edu

Dr. Brough is an employee of GenVec Inc. Dr. Staecker has a sponsored research agreement with GenVec Inc.

© 2007 Otology & Neurotology, Inc.