STEM CELLS AND OTHER NEW RESEARCH BRINGS US CLOSER TO TREATMENTS FOR THE HEARING IMPAIRED
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NR-11-05 (11/13/05). For more information, please contact Sara Harris at (202) 462-6688 or sharris@sfn.org.
STEM CELLS AND OTHER NEW RESEARCH BRINGS US CLOSER TO TREATMENTS FOR THE HEARING IMPAIRED
WASHINGTON, DC, November 13, 2005 — Ca oo er me owww? Ca ooo he eee oooo? Can you hear me now?
A cell phone caller’s voice fading in and out can be wildly frustrating. Yet this is nothing compared to what approximately 28 million Americans who have a hearing impairment experience daily. Hearing problems can make it hard to enjoy talking with friends and family even when face-to-face. They also can make it difficult to understand and follow a doctor’s advice, to respond to warnings, and to hear doorbells and alarms.
Now, however, new research that reveals the biology behind hearing as well as insights into how to repair or rebuild a damaged hearing system may soon lead to improved treatments for hearing loss that could better the lives of many.
“Breakthroughs in the field of hearing and deafness research are revealing many secrets of the inner ear,” says Jeffrey T. Corwin, PhD, a hearing expert at the University of Virginia, School of Medicine. “These discoveries could form the foundation for future therapies to treat inner ear dysfunction.”
New therapies, for example, could arise from new findings on stem cells; special cells that can make copies of themselves and give rise to new neural cells. “The primary reason that environmental and genetic factors cause deafness is that they damage and destroy inner ear sensory cells, called hair cells, that lack the ability to regenerate,” says Stefan Heller, PhD, of Stanford University. “But we now have found evidence that we can manipulate inner ear stem cells to replace lost sensory cells in the hearing system.”
Recently Heller’s team identified stem cells that can be coaxed into turning into the ear’s sensory cells hiding deep in the organs of hearing and balance. First they discovered stem cells in the vestibular system of the inner ear. “Our research now indicates that they are also in other parts of the inner ear, including the cochlea,” says Heller.
Additional work indicates that transplants of these stem cells can mend a damaged hearing system. The researchers transplanted batches of the stem cells into developing chick embryos and found that they developed into sensory cells in the chicks’ hearing systems. As a next step they are now using a microinjection technique to transplant stem cells into the developing inner ear of deaf mice to see if they give rise to healthy sensory cells and improve hearing function after birth. “Our research suggests that in the future we may be able to use stem cell techniques to aid hearing problems,” says Heller. “Nevertheless, the devil is in the details and we will spend the upcoming years first figuring out whether stem cell-based therapies are suitable for restoring hearing loss in laboratory animals.”
Other new work also may lead to ways to help deaf patients grow new inner ear tissue and regain their sense of hearing. “We discovered genes and proteins that are critical for the proper formation and orientation of the sensory cells and other cell types in the ear,” says Matthew Kelley, PhD, of the National Institute on Deafness and Other Communication Disorders. Specifically, work in animal models revealed that the molecules, termed Van Gogh like 2 and Scribble 1, play key roles in engineering the hearing system’s unique labyrinthine structure during development and orienting the ear’s sensory cells.
“Understanding how and when these molecules function is necessary for a better understanding of the types of deafness that are present at birth,” says Kelley. It’s also possible that the discoveries could aid researchers in finding ways to rebuild ear tissue in a wide range of people with hearing impairments. “Correct orientation of the sensory cells is required for normal function, therefore any effort to rebuild, or regenerate lost sensory cells must include an understanding of their orientation, because otherwise they will not function correctly,” says Kelley. As a next step, the researchers plan to determine how the molecules, Van Gogh like 2 and Scribble 1, actually function at the cellular level to direct the orientation of the sensory cells.
Other findings provide new details on how the ear normally hears in an effort to determine ways to repair problems in those with hearing impairments. An inner ear protein called TRPA1 is crucial for proper hearing, according to research by Jeffrey R. Holt, PhD, of the University of Virginia’s School of Medicine, who chairs a mini-symposium on hearing at this meeting. Specifically, this central molecule in the ear helps the ear’s sensory cells convert sound into electrical signals. These signals are then sent via the auditory nerve to the brain for interpretation, allowing us to hear.
First, Holt and his colleagues determined through cell studies and tests in animal models that the gene TRPA1 and the protein it produces is a key component of the hearing system. “The discovery marks the end of a 25 year search for the elusive molecule and the beginning of a new era for inner ear research,” says Holt.
Most recently, the researchers discovered how the protein operates. “The TRPA1 protein appears to be shaped like a donut with a hole in the middle,” says Holt. In silence the hole is blocked. When sound strikes the molecule, the hole pops open and potassium and calcium molecules flow through the hole into the ear’s sensory cells, which in turn, generate an electrical signal. “The identification of this gene and protein required for normal hearing is a step toward helping us find ways to one day, restore auditory function in deaf patients,” says Holt. “The identification also presents a new target geneticists can screen to diagnosis patients with hereditary hearing loss.”
Other scientists determined that sensory receptors in sensory cells of the inner ear not only sense sound but also actually move and generate mechanical force, probably to amplify softer sounds.
To understand speech, sounds must be processed accurately and at high speed, according to the lead author of the work, Helen Kennedy, PhD, of Bristol University in the United Kingdom. However, in order to achieve the high levels of sensitivity required for hearing sounds such as speech, the sound vibrations must be amplified in some way. The sensory cells of the inner ear have specialized structures, or hair bundles, that sit on top of the cells. “As sound comes into the ear it causes the fluids of the inner ear to vibrate in time with the stimulus,” says Kennedy. “The sensory hair bundles can detect these small mechanical vibrations and convert them into electrical signals.”
In their study, the researchers used rats to closely examine this hearing process. They stimulated the animals’ sensory hair bundles and recorded how the cells responded. “We found that the sensory hair bundles were capable of responding fast enough to follow a high frequency stimulus very accurately,” says Kennedy. “In addition the sensory hair bundles could actually amplify this stimulus by generating their own movements and substantial mechanical forces in time with the stimulus.” The researchers also found that these movements were generated within the sensory hair bundle itself and were linked to activity within tiny channels at the tips of the sensory hair bundles. “The mechanism probably functions to amplify very soft sounds, such as whispers, and allows the ear to distinguish one pitch from other similar pitches,” says Kennedy.
As a next step, she plans to identify how this system is modulated and the genes and proteins that contribute to the mechanism.
In other work, scientists discovered how the sensory cells in the ear communicate with the auditory nerve that carries the electrical impulses to the brain. “We discovered how this unique connection transmits auditory information at the very high and continuous rates needed to enable hearing,” says Elisabeth B. Glowatzki, PhD, of Johns Hopkins University.
To detect sound and transmit it to the brain, the inner ear has to transform a mechanical wave into an electrical signal. Sensory cells in the inner ear perform this transformation and subsequently release little packets of chemicals (transmitter) onto auditory nerve fibers. The transmitter activates electrical signals in auditory nerve fibers, and information about sound travels through these fibers to the brain.
With powerful microscopes and highly sensitive amplifiers, the scientists studied electrical activity in auditory nerve fibers from rat inner ear tissue that was dissected and kept alive and functioning for a few hours. Most nerve cells in the brain release one packet of transmitter at a time. However, Glowatzki and her colleagues found that sensory cells in the inner ear send out multiple packets of transmitter at once, activating unexpectedly huge signals in the auditory nerve fibers.
This year her group also discovered specific ion channels located in auditory nerve fiber endings directly where they contact the sensory cells. Ion channels are tiny gates in the nerve fiber membrane that can pass potassium, sodium or calcium molecules and thereby can change the electrical signal in the nerve fiber. These ion channels modulate the electrical signals in auditory nerve fibers so that higher frequency signaling in the auditory nerve can occur, an important feature for normal hearing. “The better we can understand how electrical activity is coding sound in the auditory nerve, the better we will be able to improve the accuracy, by which hearing aids and cochlear implants can work,” says Glowatzki.
