A new gene therapy approach has led to the first major success story in the ongoing effort to develop techniques countering deafness due to inner ear damage.

Highly specialized epithelial cells known as 'hair cells', located within an inner-ear structure called the cochlea, have a central role in the mammalian auditory system, in that they are directly involved in translating the vibrations from sound waves into signals that can be interpreted by the brain. Damage to these cells can have a profound effect on hearing, and degeneration and loss of hair cells—from causes both natural and unnatural—is among the more common reasons for onset of deafness. Importantly, the body does not replace lost hair cells on its own, leaving the onus on researchers to develop strategies for the restoration of these valuable cells.

A group of American and Japanese researchers, led by Yehoash Raphael at the University of Michigan (Ann Arbor), have stepped up to the challenge, focusing their attention on Atoh1, a gene known to be important in the differentiation of hair cells during embryonic development. Previous studies have indicated that the action of Atoh1 can induce nonsensory cells in the cochlea to generate new hair cells; Raphael and his colleagues now sought to find out whether the viral-mediated transfer of this gene to the inner ears of deafened guinea pigs could help restore hair cell growth and hearing (Nat. Med., March).

They chemically deafened the animals in a manner that eliminated virtually all hair cells and then treated the damaged cochleas with an adenoviral vector containing the Atoh1 gene. Effective transduction of the gene into and expression by the nonsensory cells of the cochlea took place, and within 8 weeks, large numbers of hair cells were detectable, with the most effective restoration occurring near the site of injection.

There are two basic types of hair cells: outer cells (OHCs), which amplify vibratory signals, and inner cells (IHCs), which actually convey information to the brain via the auditory nerve. This gene therapy approach proved most effective at IHC restoration, and these cells became fully differentiated and relatively well organized; the OHCs, on the other hand, generally failed to reach full maturation. Nevertheless, by 8 weeks, the treatment had restored a considerable amount of acoustic sensitivity to the animals, as determined by a commonly used hearing test, and this recovery remained constant for at least several weeks afterward.

The researchers speculate that Atoh1 might trigger mature nonsensory cells in the cochlea to proliferate and redifferentiate as hair cells, or that perhaps the cochlea contains an undiscovered trove of stem cells that respond to this gene. Clearly, much more investigation will be necessary, but these early findings at least offer new promise for the restoration of lost hearing.