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In the mammalian auditory system, sensory cell loss resulting from aging, ototoxic drugs, infections, overstimulation and other causes is irreversible and leads to permanent sensorineural hearing loss. To restore hearing, it is necessary to generate new functional hair cells. One potential way to regenerate hair cells is to induce a phenotypic transdifferentiation of nonsensory cells that remain in the deaf cochlea. Here we report that Atoh1, a gene also known as Math1 encoding a basic helix-loop-helix transcription factor and key regulator of hair cell development, induces regeneration of hair cells and substantially improves hearing thresholds in the mature deaf inner ear after delivery to nonsensory cells through adenovectors. This is the first demonstration of cellular and functional repair in the organ of Corti of a mature deaf mammal. The data suggest a new therapeutic approach based on expressing crucial developmental genes for cellular and functional restoration in the damaged auditory epithelium and other sensory systems., Author(s): Masahiko Izumikawa [1, 2]; Ryosei Minoda [1, 3]; Kohei Kawamoto [2]; Karen A Abrashkin [1]; Donald L Swiderski [1]; David F Dolan [1]; Douglas E Brough [4]; Yehoash Raphael [...]

Genetic mapping has refined DFNB3 (ital), the nonsyndromic congenital recessive deafness gene, to 17p11.2 and suggested multiple alleles of DFNB3 (ital). It also supports homology to the mouse model shaker-2 (ital). DFNB3 (ital) was first identified in a village in Bali in Indonesia. Affected individuals from that village and from a neighboring village have been found to be homozygous for the same alleles for six adjacent short tandem repeats (STRs) in the DFNB3 (ital) region and heterozygous for other distal markers. Nonsyndromic deafness in two unrelated consanguineous Indian families were linked to the same region. DFNB3 (ital) appears to make a significant contribution to hereditary deafness in the world.