Plenary Session: What's on the Drawing Board?
Editor: Dr. Edwin Rubel gave a great presentation on research aimed
at preventing and treating hearing loss. Here's a report from NVRC's
Cheryl Heppner.
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New Approaches Toward Prevention and Remediation of Hearing Loss
Presenter: Dr. Edwin W. Rubel, the Virginia Merrill Bloedell
Professor of Hearing Science, Departments of Otolaryngology,
Neurosurgery, Physiology and Biophysics, and Adjunct Professor of
Psychology, University of Washington, Seattle
Dr. Rubel gave a very upbeat and entertaining presentation on recent
research aimed at treating and preventing hearing loss, hair cell
regeneration, and understanding how hair cells die. Here are some of my
notes:
- What do we do when hair cells are damaged, causing hearing loss? We
can use a cochlear implant to bypass the problem or use a hearing aid to
try to stimulate the remaining hair cells harder.
- Birds can recover to normal or near normal after hearing loss. He
first learned about birds in 1987-88 and why their hearing is a terrific
model to study. Their ears work the same way ours do, but are straight
and have a shorter cochlea. In a 1987 study, loud sounds were played and
it was found that cells in the bird cochlea were damaged and dying. Five
days later, new "baby cells" were coming up. Then we learned
that in birds, new hair cells are produced and proliferate, growing five
times as fast in the first days after the damage.
- Did the new hair cells that these birds grew actually work? In a
study that used starlings, damage was created, the birds grew new hair
cells, and then more damage was created to learn this. One of the birds
that helped show that those new hair cells work is the Bengalese finch,
which learns its song from its father. When it becomes deaf, the song
deteriorates. In these finches, when the cells were regenerated, its
song came back because it could hear itself.
- Humans and all mammals are not so great at this; they have very
little hair cell proliferation. There were three theories why: 1. There
is no mother cell, so no cell is capable of division 2. There is no
trigger for cell division 3. Something inhibits cell growth
- The mother cell theory was debunked when hair cells were taken from
mice and successfully treated with a growth factor. Many experiments and
combinations have been done in vitro or in tissue culture to find a
trigger for cell division. We now know there is such a trigger but still
need to find the appropriate trigger.
- We've learned that in mice the P-27 gene has showed success. We
also know there is heavy blockage of cell division in mammals.
- We must remember that mammal brains are really good, so all we need
is a few hair cells, just as we need a few channels in our cochlear
implants.
- Recently scientists began thinking that it would be better if we
could just learn to prevent hair cell death and thus prevent hearing
loss. More attention is being given to discovering why cells die so we
can interrupt the process.
- A zebra fish study has allowed scientists to follow pathways of
inhibitors. Aminoglycosides can be used, as they follow a particular
pathway. If we understand this process, then we can enter it and prevent
it from happening. By learning this, we may be able to delay hearing
loss 10 or 20 years, or permanently. A zebra fish has genes that are 85%
identical to ours. Its hair cells are exposed, which aids study because
there is no need to dig around inside them; instead studies can be done
directly on the live animal.
- What is on the drawing board is bright. He feels positive about the
eventual treatment of hearing and balance disorders.
Q: Isn't the cat closest to a human? When will studies switch from
zebra fish to cats? A: Most research has been done on cats, but the cat
isn't closer than the gerbil or a rodent. Most mammal ears are similar.
Live animal studies are very time consuming.
Q If hearing is destroyed, restored, then destroyed, then restored,
is there a point at which it doesn't come back or deteriorates? A: Yes,
all cells have a proliferation life line. If you keep destroying them,
especially through a toxic substance, eventually you destroy the mother
cell.
Q: Vestibular cells are being used, not cochlea cells will the
cochlea cells be harder to regenerate? A: Yes, they are resistant. It's
not a question of if, but WHEN cells will be able to regenerate. The
only thing holding us back is money. Vestibular structure is a very
highly conserved system across species of mammals. The cochlea has been
resistant, so vestibular cells are used because they can be tested in
adult animals. Cochlea cells can't be kept in culture. If we can just
make 100 hair cells in the cochlea, the brain would do the rest.
Q: Has any research been done on nerve cells to aid in stopping
sensorineural hearing loss? A: Nerve deafness is actually almost always
due to the loss of hair cells. Temporal bones of deaf people examined
after death show quite a few ganglion cells but not hair cells.
Q: What is research showing about toxic drugs? A: The FDA doesn't
test drugs for ototoxicity because it's felt most drugs affect the high
frequency hearing. Most hearing tests don't consider the highest
frequencies. Up until recently there has been no good test for
toxicology. The zebra fish will probably be a good model. Drug
interactions should be important information to the FDA.
Q: What about side effects? A: There is nothing special about hearing
in birds but there is something special about mammals. We still
regenerate our skin, muscles, and fat but not those hair cells. A
favorite hypothesis is that we are basically a low-frequency hearing
animal, evolved to focus on that. Birds are specialists in the high
frequencies. Think of piano strings and how they are tuned. They are
still in the high frequency tones.
Q: Could man be suffering the side effects of the advance of
civilization such as noise and drugs? A: Yes, there is no question these
factors interact with genetics. we also suffer because we live longer.
There are many factors -- nutrition, medicine, social conditions, and
stresses on our society to be healthy. Hearing research receives less
money than virtually any other kind because hearing loss is not a
life-threatening condition. But we get to a point in our lives where
most of us have hearing loss.
Q: What is the time frame for regeneration of cells? A: It's going to
depend on the funding. Discovery research is targeted and can be done on
small budgets. The advances like regeneration need an industry approach.
Give me $10 million to give to five labs with different expertise and we
could tell you in five years. But no federal funding agency will give
this money. We need targeted approaches. Once they show results, drug
companies will get involved in a snap. People need to go to Congress and
ask for a great deal more money for this research for NIDCD at the
National Institutes on Health.
