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MGH researchers find way of regenerating
cells key to hearing
Finding someday may help treat hearing
loss, neurodegenerative disorders
BOSTON - January 13, 2005 - Selectively turning off a protein
that controls the growth and division of cells could allow regeneration
of the inner ear's hair cells, which convert sound vibrations into
nerve impulses. The discovery by a research team based at Massachusetts
General Hospital (MGH) runs counter to current beliefs about these
cells and could eventually lead to ways of preventing or treating
hearing loss. The report will appear in the journal Science
and is receiving early online release on the Science Express website
at http://www.sciencexpress.org.
"These findings give us a potential strategy for hair cell
regeneration, which could have enormous implications for the treatment
of hearing and balance disorders," says Zheng-Yi Chen, DPhil,
of the MGH Neurology Service, the study's senior author. "It
also shows that cells that have been considered incapable of regeneration
- like most nerve cells - can reproduce under the right conditions,
which may have applications to neurodegenerative diseases."
Named for the hair-like projections on their surfaces, hair cells
form a ribbon of vibration sensors along the length of the cochlea,
the organ of the inner ear that senses sound. Receiving sonic vibrations
through the eardrum and bones of the middle ear, hair cells convert
them to electrical signals that are carried to the brain by the
auditory nerve. Among the earliest structures to form in embryonic
development, hair cells are very sensitive to damage from excessive
noise, infections or toxins including some medications. Once damaged,
hair cells do not naturally regenerate in mammals, and their death
accounts for most types of acquired hearing loss.
Cells grow and divide through a process called the cell cycle, and
many proteins have been indentified as controllers of the different
cell cycle phases. Chen's group started by carrying out a comprehensive
assessment of which genes are active in the developing mouse ear
and when they are expressed. The activity of certain genes suggested
that the retinoblastoma (Rb) protein, known to suppress the cell
cycle, could be important for halting the cell cycle in hair cells.
To follow up that observation, the researchers used a genetically
modified mouse strain in which Rb was no longer made in the inner
ear.
They found that hair cells in the ears of these mice were significantly
more numerous than in normal mice at the same stage of development.
These additional cells retained the distinctive appearance of hair
cells, performed functions characteristic of normal hair cells and
appeared fully able to form proper connections with nerve cells.
In addition, hair cells in the modified mice made proteins that
indicated they were still actively regenerating, while cells in
normal animals did not.
The researchers note that these findings will form the basis for
the future work aimed at recovery of hearing through hair cell regeneration.
In particular, they have to learn to control the presence of Rb
for short times, allowing some regeneration but not too much. The
genetic basis of hearing and deafness is almost identical in mice
and in humans, so a successful mouse model may ultimately translate
into therapy in human patients.
"It's taken over 10 years of work to show that hair cells can
regenerate in tissues, and I hope it won't take another decade to
achieve functional regeneration in a living animal," says Chen.
"But my hope and belief is that, if we can do this in mice,
we'll be able to achieve it in people." Chen is an assistant
professor of Neurology at Harvard Medical School (HMS).
The report's co-authors are first author Cyrille Sage, PhD, and
Mingqian Huang, PhD, of the MGH; Kambiz Karimi, PhD, and Jeffrey
Corwin, PhD, University of Virginia School of Medicine; Gabriel
Gutierrez, PhD, and Philip Hinds, PhD, Tufts-New England Medical
Center; Jaime Garcia-Anoveros, PhD, Northwestern University; and
Melissa Vollrath, PhD, Duan-Sun Zhang, PhD, and David Corey, PhD,
Howard Hughes Medical Institute and HMS. The study was supported
by the National Institutes of Health and a Pfizer/AFAR Innovations
in Aging Research Grant.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $400 million
and major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham
and Women's Hospital joined to form Partners HealthCare System,
an integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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