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Year : 2001  |  Volume : 3  |  Issue : 11  |  Page : 37--47

Gene-based therapy for inner ear disease


Kresge Hearing Research Institute, The University of Michigan Medical School, Ann Arbor, USA

Correspondence Address:
Yehoash Raphael
Kresge Hearing Research Institute, The University of Michigan Medical School, Rm. 9303, MSRB 3, Ann Arbor, MI 48109-0648
USA
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Source of Support: None, Conflict of Interest: None


PMID: 12689447

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Environmental inner ear insults often lead to hair cell injury and loss. Therapeutic measures for the prevention of hair cell loss are currently limited. Several reports have demonstrated the applicability of growth factors for hair cell protection. The goal of the experiments presented here was to assess the protective capability of the human GDNF transgene against noise trauma in the guinea pig cochlea. The left ears of guinea pigs were inoculated with a recombinant adenovirus with a human GDNF insert (Ad.GDNF). Four days later, animals were exposed to noise trauma. One week later, animals were sacrificed and hair cells counted in the left (inoculated) and right (non-inoculated) ears. Auditory brainstem thresholds were measured before the inoculation and just prior to sacrifice. Control groups included inoculation with a reporter gene vector (Ad.lacZ) and Ad.GDNF in normal ears with no noise exposure. The results show that intracochlear inoculation with adenovirus into normal ears does not compromise hair cell counts and ABR thresholds. Both Ad.GDNF and Ad.lacZ vectors can protect the cochlear hair cells and hearing from the noise insult. The difference between the protection afforded by Ad.GDNF and that of the Ad.lacZ vector is not statistically significant. The mechanism of Ad.lacZ protection needs to be elucidated. The data demonstrate the general feasibility of gene therapy for over-expression of neurotrophic factors against noise trauma, and emphasize the complexity of the technique and the problems of variability between subjects.






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