Researchers at Harvard University have shown that genome editing might offer a solution to deafness after successfully restoring partial hearing in mice using the method.
Some people lose their hearing without doctors being able to explain what exactly went wrong. Hearing loss can affect anyone, but it is more common among people who are at least 12 years old. Disabling hearing loss is most common among the elderly.
Deafness, of varying degrees, affects millions of people in the United States. Estimates have it that roughly 13 percent of people aged 12 years or older have hearing loss in their two ears.
Hearing aids and other helpful technologies are available for dealing with the problem to an extent. However, these do not cure deafness or restore hearing.
The new Harvard study published in Science Translational Medicine raises hope that it might be possible to cure deafness in the future. Researchers were able to restore partial hearing in mice by correcting a recessive mutation resulting in deafness.
Dominant and recessive mutations
Two main types of mutations occur in deafness and genetic diseases: dominant and recessive mutations.
A dominant mutation is one that affects only one of the two gene copies in the body. Diseases resulting from this sort of mutation may be rather easier to combat. The main thing to do is just to get rid of the bad copy for the good one to do its job.
Two of the scientists in this new study were able to repair a dominant mutation and prevent hearing loss in research carried out two years ago. It was the first time such a feat would be achieved.
“Most genetic diseases are not caused by dominant mutations, they’re caused by recessive ones, including most genetic hearing losses,” explained David R. Liu, Thomas Dudley Cabot Professor of the Natural Sciences at Harvard.
Liu is one of the researchers in the current study that repaired deafness-causing dominant mutation in mice years ago. The other is Wei Hsi Yeh, a recent Ph.D. in Chemistry graduate from Harvard, who chose this line of research as a result of a rather sudden total hearing loss suffered by a friend.
Unlike a dominant mutation, a recessive mutation refers to the existence of two bad gene copies. Liu said this makes a disorder impossible to correct by simply eliminating the bad copy. The only solution would be to restore at least one of the two copies to a good state.
Restoring hearing through gene editing
Hair cells in the ear aid hearing in animals. Pressure from sound waves causes them to bend, sending electrical signals to the brain to enable hearing.
A recessive mutation to the gene TMC1 in mice results in total hearing loss. Researchers say that the mutation causes hair cells to degrade very fast to cause complete deafness in the animals at only 4-week-old.
It took the Harvard scientists years to build a base editing technology that could be used to correct recessive mutations. After designing a seemingly viable base editor to correct defective gene copies, Yeh had to contend with the issue of it being too bulky to fit into an adeno-associated virus (AAV), the conventional vehicle for delivery.
The researchers decided to divide the base editor into two halves to get over the unwieldiness challenge. A different virus was used to deliver each half. The two halves rejoined after gaining entry and then get down to work.
Completely deaf mice displayed at least partial hearing following treatment with this technology. The animals jumped and look in Yeh’s direction when she clapped her hands. They responded to loud sounds and, in some cases, to medium sounds.
It was the first time scientists would successfully restore hearing by correcting a recessive mutation with genome editing.
The base editing technology proved very effective, with minimal unwanted deletions. This study also confirms that the AAV delivery technique can really help in the drive to combat genetic disorders.
Researchers in this study observed that cells that were not edited continued dying, making deafness come back. They expressed the need for further research before this method could be used for treating humans.