Gene therapy grows new auditory hair cells ...( he inner ear of a guinea pig is so smal...)

he inner ear of a guinea pig is so small, the mechanical impact of injecting the viral vector fluid into the cochlear fluid damaged some of the hair cells in experimental animals. "While this is a concern, we believe the micro-injection technology can be improved to prevent this mechanical trauma," Raphael says. "The human cochlea is larger than a guinea pig cochlea and may better tolerate the inoculation. Also, profoundly deaf human candidates for this gene transfer approach would likely have severe pre-existing hair cell loss to begin with, so the risk of mechanically-induced side effects would be somewhat less troubling."

One of the most surprising results of the study was the discovery of long, slender nerve fibers growing toward some of the newly formed hair cells. "This suggests that these hair cells can provide signals to attract axons and that neurons can respond to these signals," Raphael says.

In the next stage of research, Raphael will determine whether the guinea pig hair cells are functional and able to transmit sound signals to auditory neurons. He also plans to test the procedure in aging animals and in animals that are completely deaf.

"This is just the beginning," Raphael says. "It is really just a proof of the principle to show that, with proper gene therapy, these non-sensory cells have the competence to become hair cells."

The research was funded by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health and supported by GenVec, Inc. GenVec provided its proprietary adenovector technology to deliver the atonal gene, Math1. Raphael was an occasional consultant to GenVec, but has no significant financial interest in the company.

First author on the paper was Kohei Kawamoto, Ph.D., a former U-M research fellow who is now at Kansai Medical University in Osaka, Japan. Co-authors on the paper include Douglas E. Brough, Ph.D., director of vector sciences at GenVec,
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Contact: Sally Pobojewski
pobo@umich.edu
734-615-6912
University of Michigan Health System
31-May-2003

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