More than 28 million people in the U.S. suffer some form of hearing loss. One of the most common origins of hereditary hearing loss in children, not only in the U.S. and Europe, but also in China, Japan, and Korea, is mutation of the SLC26A4 gene.

Now, a Kansas State University research project that investigated that precise gene shows potential to treat human deafness and loss of balance.

How does the ear function?

The SLC26A4 gene 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. The cochlea is a snail-shaped structure that helps process sound. The vestibular aqueduct is a bony canal that connects the inner ear with the brain cavity.

Although it is known that the SLC26A4 provides instructions for making a protein called pendrin, the significance of pendrin is not fully understood. Researchers have suggested particular roles for pendrin. For instance, within the inner ear, it is likely that pendrin helps control the proper balance of charged particles like chloride and bicarbonate ions. Maintaining the correct level of these ions is critical for the hearing process as well as for determining the amount of fluid that bathes the inner ear. In turn, this fluid level appears to be important during development of the inner ear, and it may even influence the shape of the cochlea and vestibular aqueduct.

"In my research, I have been interested in how the inner ear functions," said Philine Wangemann, lead author of the study and professor of anatomy and physiology at the College of Veterinary Medicine. "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."

To accomplish these objectives, Wangemann and her global team generated a transgenic mouse.

Mutant Mice

When the mutant mice lack SLC26A4 expression, their inner ears swell during embryonic development. This leads to failure of the cochlea and the vestibular organs, resulting in deafness and loss of balance. The multitude of sites where SLC26A4 is located made the goal to restore function look futile — on which site do you focus? — unless some sites are more important than others. After reviewing past research, Wangemann and her team understood exactly where to aim: the endolymphatic sac.

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

Additionally, the restoration of hearing and balance lasted for the duration of the testing period, which suggests that the achieved effect of repaired hearing may be 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 hearing and balance," said Wangemann. She noted that the foundation for her research is the fact that the human disease — hereditary hearing loss — may be replicated in a mouse model.

Human Losses

Although these findings only provide evidence within the model of transgenic mice, Wangemann explained that the idea is to eventually develop a pharmacological treatment for human patients. Much more research will be necessary, though, including studies that help scientists understand how fluid secretion and absorption are supported and how the balance of secretion and absorption is maintained to prevent the detrimental swelling.

The Centers for Disease Control and Prevention estimates that genetic factors are responsible for hearing loss among 50 to 60 percent of children with hearing loss. Of these, about 20 percent of babies with genetic hearing loss have a "syndrome" (for example, Down syndrome or Usher syndrome). Among almost 30 percent of babies with hearing loss, however, infections in the mother during pregnancy, other environmental causes, and complications after birth are responsible for a child's loss of hearing.

Source: Wangemann P. SLC26A4Targeted to the Endolymphatic Sac Rescues Hearing and Balance in SLC26A4 Mutant Mice. PLOS Genetics. 2013.