University of Michigan scientists have used gene therapy to grow new auditory hair cells in adult guinea pigs. This discovery could lead to new treatments for human deafness and age-related hearing loss.

Since the discovery in the late 1980s that birds can spontaneously regenerate damaged hair cells, scientists have been trying to find a way to induce the replacement of lost hair cells in mammals. University of Michigan scientists have now accomplished this goal by inserting a gene called Math1 into non-sensory epithelial cells lining the inner ear. Results from the study were published in the June 1 issue of the Journal of Neuroscience ["Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo," Vol. 23].

"We found that non-sensory epithelial cells in adult guinea pig cochlea can generate new sensory hair cells following the expression of Math1," said Yehoash Raphael, PhD, an associate professor of otolaryngology in the University of Michigan Medical School. "We also found that some of these hair cells can attract the growth of new fibers from auditory neurons," said Dr. Raphael, who directed the study.

Math-1 Overexpression Causes Transdifferentiation

"During the embryonic stage of an animal's development, hair cells and supporting cells have a common origin. Cells that express Math1 are fated to become hair cells, while Math1 expression is inhibited in the remaining non-sensory cells," Dr. Raphael noted.

"After embryonic development, hair cell production ceases. Unlike other epithelial cells in the skin or gut, epithelia in the inner ear contain no stem cells, so there is no source for renewal," Dr. Raphael explained. "That's the main reason why hair cell loss is permanent. When we over-expressed Math1 in non-sensory cells of the mature cochlea, however, we found that it causes them to transdifferentiate, or change their personality to become hair cells."

"We knew that transdifferentiation of supporting cells was a major source of new hair cell development in birds," Dr. Raphael noted. "But there was no proof it would work in mammals. We started gene therapy experiments in 1994 and it took us seven years to develop a successful method of introducing the gene into the non-sensory cochlear epithelium."

Kohei Kawamoto, PhD, a former University of Michigan research fellow who performed the laboratory experiments, used an adenovirus as a vector to deliver the Math1 gene to inner ear epithelial cells. Kawamoto injected the Math1 vector into inner ear fluid of 14 adult guinea pigs. The same procedure, but without the transfer of the Math1 gene, was performed on 12 matched control animals.