SWIDERSKI, D.L.*; IZUMIKAWA, M.; BROUGH, D.; RAPHAEL, Y.; Univ. of Michigan, Ann Arbor; Univ. of Michigan, Ann Arbor; GenVec, Gaithersburg, MD; Univ. of Michigan, Ann Arbor: Regeneration of sensory cells in the inner ear of deafened mature guinea pigs

The mammalian organ of Corti, the sensory epithelium of the inner ear, is a mosaic composed of sensory cells (hair cells) and non-sensory supporting cells. All cells are highly differentiated in structure and function. Because no undifferentiated cells are held in reserve to replace damaged cells, hearing impairment due to loss of hair cells is permanent. Differentiation of complex tissues like the organ of Corti typically is governed by specific cascades of gene expression. In mice, a critical gene in the differentiation of hair cells is the basic helix-loop-helix transcription factor Math1, a homolog of the Drosophila gene atonal. Previous studies have shown that inoculating inner ears of normal adult guinea pigs with an adenovirus vector expressing Math1 (Ad.Math1) can generate new cochlear hair cells in regions normally occupied only by supporting cells. In this study, we deafened adult guinea pigs by administration with ototoxic drugs (kanamycin and ethacrynic acid) prior to inoculating their inner ears with Ad.Math1 and evaluated differences in hair cell number and hearing thresholds before and after treatment. This research is supported by GenVec and by NIH-NIDCD grants R01 DC01634 and P30 DC 05188.