Researchers from the University of Iowa and Okayama University in Japan say the study is a proof-of-principle experiment that may point the way to new deafness treatments in humans.

"We gave a genetically-deafened mouse interfering RNA that specifically prevents a gene from being expressed that would otherwise cause deafness," says study senior author Richard Smith of the University of Iowa. "By preventing its expression, we prevented the deafness."

While the approach is in the early stages, Smith calls it "really exciting because it points to other options for people who have hearing loss other than hearing aids or cochlear implants."

A University of Iowa news release describes the gene-silencing experiment, which used RNA interference (RNAi), as follows:

To test the gene-silencing technique, Yukihide Maeda, M.D., Ph.D., a postdoctoral researcher in Smith's lab and lead author of the study, introduced a mutated gene that causes deafness in humans into the inner ear of mice. This gene acted through a dominant negative mechanism, and the mice had moderate hearing loss. Next, Maeda simultaneously introduced the mutant gene and a short piece of interfering RNA specifically designed to silence the gene. Standard hearing tests, similar to those used on newborn babies, confirmed that the treated mice were able to hear.

Smith noted that RNA interference was not only successful but also highly specific. Despite the fact that the mouse and the human gene differed by only two nucleotides over the short stretch of gene targeted by the RNAi, the mutant human gene was silenced while the normal mouse gene was unaffected.

With a view to someday moving this therapy to humans, the researchers also developed a non-invasive strategy to deliver the RNAi. A small piece of foam soaked in a solution containing the interfering RNA was placed against the membrane covering one opening into the inner ear of the mice. The slightly porous membrane allowed the interfering RNA to diffuse into the inner ear cells.

The team says the strategy should translate easily to humans, but several issues still must be addressed, including determining if the treatment will work in a mouse that has been deaf for some time and finding ways to sustain the gene-silencing effect over an extended period of time.

By Simon Smith