Helping to restore balance after inner ear disorder

Many disorders of the inner hear which affect both hearing and balance can be hugely debilitating and are currently largely incurable. Cochlear implants have been used for many years to replace lost hearing resulting from inner ear damage. However, to date, there has not been an analogous treatment for balance disorders resulting from inner ear disease. One potential new treatment is an implantable vestibular prosthesis which would directly activate the vestibular nerve by electrical stimulation. This prosthetic treatment is tested in a new study by Christopher Phillips and his colleagues from the University of Washington in Seattle, USA. Their findings are published in the Springer journalExperimental Brain Research.

Meniere’s disease is a disorder of the inner ear that can affect hearing and balance to varying degrees. The characteristic symptoms are episodes of vertigo, tinnitus, a feeling of pressure in the  and hearing loss which tends to worsen as time goes on. Although there is medication which can help once an attack is underway, there is currently no long-term therapy which can resolve the disease completely.

Phillips and his colleagues have developed a vestibular prosthesis which delivers electrical stimulation to the fluid inside the semi-circular canals of the ear. In effect, the stimulation of the fluid makes the brain believe that the body is moving or swaying in a certain direction. This then causes a compensatory postural reflex to stabilize the posture thereby helping to restore balance.

For their study, this prosthesis was inserted into the ears of four subjects all suffering from long-term Meniere’s disease and differing degrees of hearing loss which was resistant to other . After a full evaluation of each participant’s vestibular function, their eye function was measured in response to electrical stimulation along with their postural response both with their eyes open and closed.

The researchers found that  of the fluid in the semicircular canals of the affected ear did result in a change in posture, the direction of which was dependent on which ear was stimulated. However, each subject had different sway responses to the stimulation given. The authors believe this could be caused by small differences in the location of the electrode between subjects. Thus fine tuning and individual calibration for each electrode implant would be required for it to be effective.

Overall the results illustrate that this type of prosthesis may eventually be a possible treatment for balance issues caused by Meniere’s disease. However, there are a large number of matters which would need resolving before it is ready for use. The lack of consistency in direction and magnitude of sway response would require further study to ensure that any prosthesis developed could give reliable results for different individuals.

The authors conclude: “Taken together, our findings support the feasibility of a vestibular  for the control of balance and illustrate new challenges for the development of this technology. This study is a first step in that direction.”

Genetics research leads to successful restoration of hearing and balance

The sounds of success are ringing at Kansas State University through a research project that has potential to treat human deafness and loss of balance.

Philine Wangemann, university distinguished professor of anatomy and physiology in the College of Veterinary Medicine, and her international team have published the results of their study in the July issue of the journal PLOS Genetics: “SLC26A4Targeted to the Endolymphatic Sac Rescues Hearing and Balance in SLC26A4 Mutant Mice.”

“When the SLC26A4 gene is mutated, it leads to a loss of pendrin expression, which causes swelling of the inner ear and loss of hearing and balance,” Wangemann said. “In my research, I have been interested in how the inner ear functions. We worked on the idea that if you keep one domino in the chain standing, then the others would continue to stand and function normally. In other words, if we could restore the proper expression of pendrin in the endolymphatic sac and thereby prevent swelling of the sac, this may prevent swelling of other parts of the inner ear and rescue hearing and balance.”

More than 28 million people in the United States suffer some form of hearing loss. Wangemann said mutation of SLC26A4is one of the most common forms of hereditary hearing loss in children, not only in the U.S. and Europe, but also in China, Japan and Korea, which makes this research very significant on a global scale.

The foundation of Wangemann’s study is that this human disease is largely recapitulated in a mutant mouse model. SLC26A4 is normally found in the cochlea and vestibular organs of the inner ear as well as in the endolymphatic sac, which is a non-sensory part of the inner ear. When the  lack SLC26A4 expression, their inner ears swell during . This leads to failure of the cochlea and the vestibular organs, resulting in and loss of balance. The multitude of sites where SLC26A4 is located made the goal to restore function look futile, unless some sites were more important than others.

“We generated a new mutant mouse that expresses SLC26A4 in the endolymphatic sac, but not in the  or the vestibular organs of the inner ear,” Wangemann said. “Fantastically, this mouse did not develop the detrimental swelling of the  and even more exciting, the mouse developed normal hearing and balance.”

That restoration of hearing and balance lasted for the duration of the testing period, which suggests that the restoration is permanent.

“Our study provides the proof-of-concept that a therapy aimed at repairing the endolymphatic sac during embryonic development is sufficient to restore a lifetime of normal  and balance,” Wangemann said.

While these findings are made in a mouse model, Wangemann said that eventually the idea is to develop a pharmacological treatment for human patients, but much more research will be necessary, such as to understand how fluid secretion and absorption is supported and how the balance of secretion and absorption is maintained to prevent the detrimental swelling.

Even healthy-looking smokers have early cell damage which destroys necessary genetic programming

Smokers who’ve received a clean bill of health from their doctor may believe cigarettes haven’t harmed their lungs. However, researchers at Weill Cornell Medical College have found that even smokers who seem healthy have damaged airway cells, with characteristics similar to cells found in aggressive lung cancer.

The study, published today in the journalStem Cell, compared  that line the airway from healthy nonsmokers with those from smokers with no detectable lung disease. The smokers’ cells showed early signs of impairment, similar to that found in lung cancer—providing evidence that smoking causes harm, even when there is no  that anything is wrong.

“The study doesn’t say these people have cancer, but that the cells are already starting to lose control and become disordered,” says the study’s senior investigator, Dr. Ronald G. Crystal, chairman and professor of  at Weill Cornell Medical College. “The smoker thinks they are normal, and their doctor’s exam is normal, but we know at the biologic level that all‘ lungs are abnormal to some degree.”

The researchers found that in the cells lining the airways of the smokers’s lungs, genes had been turned on. These are genes that are normally expressed in developing embryos—soon after eggs are fertilized—before cells are programmed with their specific assignment. This gene is also “on” in the most aggressive, hard-to-treat lung cancers.

“We were surprised to see that the smokers were expressing these very primitive human embryonic stem cell genes,” Dr. Crystal says. “These genes are not normally functioning in the healthy lung.”

Healthy , like all of the body’s cells, have very specific assignments. Although all of the body’s cells contain the same genes, genes are only “turned on” for each cell’s defined task. Therefore, healthy lung cells only express genes related to lung function, while  express brain-specific genes. “Healthy cells are very tightly controlled. Normal cells have rules and only do certain things,” says Dr. Crystal. “In cancer, that control is lost.”

This loss of control allows cancerous cells to multiply without restraint and enables them to migrate to other organs because the genetic programming that keeps them on task is in disarray. The study found that smokers’ cells were in the very early stages of losing this control.

“When you smoke a cigarette, some of the genetic programming of your lung cells is lost,” says Dr. Crystal. “Your cells take on the appearance of a more primitive cell. It doesn’t necessarily mean you will develop cancer, but that the soil is fertile to develop cancer.”

In the study, 21 healthy  were compared to 31 smokers who had no lung disease symptoms and had normal X-rays as well as normal chest examinations. All individuals were evaluated at Weill Cornell’s Clinical and Translational Science Center and Department of Genetic Medicine Clinical Research Facility. By sending a thin tube called a bronchoscope and a fine brush into the lungs, investigators gently brushed the inside of the airways to collect cells from the airway’s lining. Researchers examined these cells, called the airway epithelium, which come into contact with cigarette smoke and are where cancer begins, Dr. Crystal says.

Routine checkups can mislead smokers into thinking cigarettes aren’t hurting their bodies. However, these results paint a different picture. “Physical examinations,  tests and chest x-rays are not sensitive enough to pick up these very early changes,” Dr. Crystal warns doctors and . “The take-home message is: Don’t smoke. Smoking is bad and if you smoke, you’re at risk.”

Additional studies are needed to determine why exposure to smoke causes these changes, so that researchers can pinpoint particular areas for designing treatments. “This study gives us clues about how cells look on the way to developing lung cancer, which can help us develop therapies,” Dr. Crystal says.

Beyond treatments, Dr. Crystal also hopes the research can lay the foundation for lung cancer prevention. Smoking is an addiction, he says, and despite high taxes and ads describing the dangers, 20 percent of the population continues to smoke. “Eventually, the goal is to develop therapies to protect the airways from cigarettes and other pollutants,” Dr. Crystal says. “Understanding these very early events will give us clues and help us develop ways to protect the lungs.”