| Math1 Gene Grows New Auditory Hair Cells Replacing damaged hair cells holds promise in fighting deafness
and hearing loss
Yehoash Raphael
Photo: Martin Vloet |
Department of Otolaryngology scientists in the U-M Medical School have used
gene therapy to grow new auditory hair cells in adult guinea pigs — a
discovery that could lead to new treatments for human deafness and age-related
hearing loss.
Healthy hair cells are vital to the ability to hear, but aging, infection,
certain medications and exposure to loud noises can damage or destroy hair
cells causing sensorineural hearing loss — a condition affecting over
30 million Americans. Since the discovery, in the late 1980s, that birds can
spontaneously regenerate damaged hair cells, scientists have been trying to
find a way to replace hair cells in mammals.
U-M 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 directed by Yehoash Raphael, Ph.D., an associate professor of otolaryngology,
were published in the June 1 issue of the Journal of Neuroscience.
Math1 expression (orange stain) in cells in and around the sensory epithelium
of the inner ear of a guinea pig after gene therapy.
Scanning electron microscope image of inner ear tissue
after Math1 gene transfer. A new hair cell is growing in a part of the
guinea pig’s
inner ear where hair cells do not normally develop.
A scanning electron microscope image showing normal guinea pig hair cells.
Photos courtesy of Kohei Kawamoto and Yehoash Raphael, University of
Michigan Medical School |
In a normal ear, vibrations from sound waves striking the eardrum are transferred
to fluid inside a snail-shaped bony organ called the cochlea, which is the
auditory component of the inner ear. When cochlear fluid moves, it stimulates
movement in thousands of tiny projections on hair cells lining the inside of
the cochlea. Moving hair cells initiate electrical signals, which are picked
up by auditory nerve fibers and carried to an area of the brain called the
auditory cortex. If hair cells are damaged or missing, electrical signals are
not generated and hearing is impaired.
“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,” Raphael says.
“
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. 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.”
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.
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.
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, Inc.; Shin-Ichi Ishimoto, Ph.D., a former U-M research fellow; and
Ryosei Minoda, Ph.D., a post-doctoral fellow in the U-M Medical School.
—SFP
An expanded version of the story:
www.med.umich.edu/opm/newspage/2003/haircells.htm
More about research in the Raphael lab:
www.khri.med.umich.edu/research/raphael_lab/index.shtml
 
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