Introduction
You're probably used to speaking slightly louder around elderly people, like your grandparents, if they're a little hard of hearing. This is a common occurrence when people reach a certain age, and may one day happen to you. But most hearing problems developed later in life are due to normal aging and environmental factors--not an inherited gene defect. Can you imagine being born deaf, and living that way your whole life?
This is the unfortunate reality for about 1 in every 500 newborns (7). Among this group of babies born with hereditary deafness, there are many different types and syndromes. A recent study offers intriguing information about a certain hearing and balance disorder, caused by defects in two genes that code for proteins in the choclea of the inner ear.
Sound travels through three separate chambers in your ear before being sent to the brain as nerve signals. Sound first enters the outer ear (the part that you can see) in sound waves (10). The sound waves travel through the middle ear, where they are turned into vibrations with the help of the ear drum (10). From there, the vibrations enter the liquid-filled cochlea (10). Cells in the cochlea are covered in tiny hair-like projections called stereocilia (4). The sound vibrations cause the stereocilia to move, translating into nerve signals that are sent to the brain, allowing you to hear (10)!
Below is a diagram of the inner ear (9).
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The Trial
In 2011, a team of researchers from Children’s Hospital Boston and the National Institute on Deafness and Other Communication Disorders (NIDCD) discovered that the proteins TMC1 and TMC2 are essential in the normal functioning of hearing and balance.
The trial was led by Jeffrey Holt, Ph.D., of Children's Hospital Boston and Andrew Griffith, M.D., Ph.D., of the NIDCD, and funded by the NIDCD. The findings were published in the November 21st issue of the Journal of Clinical Investigation.
The trial, conducted on mice, establishes that the proteins TMC1 and TMC2 help generate a hearing signal to the brain. TMC1 and TMC2 are part of ion channels, which allow electrically charged molecules or ions into a cell (3). These channels help to translate sound vibrations into the electrical (nerve) signals which are sent to the brain allowing us to hear. The ion channels sit on the stereocilia of the hair cells (4).
Below is a close-up of rows of stereocilia on a hair cell (8).
When mutated, the TMC1 and TMC2 genes are unable to create their essential proteins, and thus there is no way to transmit signals to the brain, causing deafness.
The researchers genetically altered mice to lack either one or both of their TMC1- and TMC2-producing genes (4). Using various techniques, they observed symptoms of deafness and dizziness in the genetically altered mice. Mice lacking just TMC2 had neither balance nor hearing problems(4). Mice lacking just TMC1 had hearing issues but no balance problems (4). Mice lacking both were deaf and had balance issues (4).
The scientists looked at electrical activity in the mice's inner ears to search for currents that relay hearing signals. Mice missing both TMC1 and TMC2 lacked currents in their inner ear cells, which correlates with inability to hear and balance normally (4).
Upon confirming their belief that, in combination, TMC1 and TMC2 are responsible for hearing loss and lack of balance, the researchers used a gene therapy technique to insert TMC1 and TMC2 proteins back into the mice's ears (4). This restored the mice's electrical response ability (3), which could mean restoration of hearing, as the electrical currents in the inner ear are necessary to relay hearing signals to the brain. The hope is that one day, hereditary deafness caused by mutations in the TMC1 and TMC2 genes will be treatable (2).
What's Next? The trial shows that TMC1 and TMC2 genes and the proteins they encode for are necessary components in the ability to hear normally (1). The researchers hope to discover more about the ways in which these proteins interact in the inner ear, as well as the roles of other proteins in the inner ear. Their success with the gene therapy techniques shows promise for eventual tests on humans. Next they will collaborate on a gene therapy trial with the Swiss Ecole Polytechnique Fédérale de Lausanne (EPFL), with whom Children's Hospital researchers recently received a $600,000 grant (3). James F. Battey, Jr., M.D., Ph.D., director of the NIDCD, said the purpose of the study was to "identify genes and proteins that are critical for normal hearing. Now our efforts appear to be paying off."(4). The study seems to have achieved its goals--and more, with the possible hope of future treatments. So while your hearing-impaired grandparents may always have trouble with their aging ears, there is a possibility that those born with a TMC1- and TMC2-related condition may not! Bibliography 1. Kawashima, Y. Géléoc, G. (December 1, 2011) Mechanotransduction in mouse inner ear hair cells requires transmembrane channel–like genes. The Journal of Clinical Investigation. 121: issue 12 2. Lin, X. (December 1, 2011) Perception of sound and gravity by TMC1 and TMC2. The Journal of Clinical Investigation. 121: issue 12 3. Children's Hospital Boston http://www.childrenshospital.org/newsroom/Site1339/mainpageS1339P804.html 4. National Institute on Deafness and Other Communication Disorders http://www.nidcd.nih.gov/news/releases/11/Pages/112111.aspx 5. Marcovitz, H. Gene Therapy Research. San Diego: Reference Point Press. 2011. 8. National Institutes of Health News http://www.nih.gov/news/pr/jun2006/images/OHC_stereocilia_illustratio.jpg 9. University of Virginia School of Medicine. http://www.medicine.virginia.edu/clinical/departments/otolaryngology/1_clincialservices/for-patients/images/CI_Anatomy.bmp |
