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Study: New Gene-Delivery Therapy Restores Partial Hearing In Deaf Mice

Sensory hair cells in the cochlea of a Beethoven mouse treated with TMC2 gene therapy. (Image courtesy: Google)

By using a novel form of the gene therapy, scientists from Harvard Medical School and the Massachusetts General Hospitals have managed to restore partial hearing and balance in mice.

They have done this with mice which were born with a genetic conditions which is affecting both.

Newer model Is overcoming a long standing barrier which is accessing hair cells. The delicate sensors over the inner ear which is capturing sound and head movement and is further converting them to neural signals for hearing and balance.

These specific cells have been notoriously difficult for treatment with the previous gene-delivery techniques.

Gene therapy restores hearing in deaf mice, paving the way for human treatment. (Image Courtesy: Google)
Gene therapy restores hearing in deaf mice, paving the way for human treatment. (Image courtesy: Google)

Notable Gains in Mice:

These findings which is published in the February issue of Molecular Therapy is showing the treatment is leading to notable gains over hearing and is allowing mice which would normally be completely deaf for hearing the equivalent of a loud conversation. This specific approach has also improved the animals sense of balance.

Accompanying commentary to the study is appearing in the same issue. Investigators are questioning the approach which is years away from the use in humans. Yet the gene therapy is carrying a promise of restoring the hearing in people which are having several forms of both genetic and acquired deafness.

About 30 million Americans are suffering from hearing loss and about every year one in 1,000 babies are born with hearing impairment, according to the Centers for Disease Control and Prevention. Over their quest for restoring hearing via gene therapy, scientists have long sought ways of improving gene delivery into the hair cells.

Previous approaches were only effective marginally as they reached one set of hair cells in the inner ear, yet another subset which is equally critical for hearing has remained largely impenetrable.

Neurologist David Corey who is a co-senior investigator over the study and the Bertarelli Professor of Translational Medical Science at HMS says, “To treat most forms of hearing loss, we need to find a delivery mechanism that works for all types of hair cells.”

Use of AAV:

For achieving that, researchers have used the common Adeno-associated Virus (AAV). This virus has been already used as a gene-delivery vehicle for retinal disorders but thus far has proven far less efficient in penetrating hair cells.

For super-charging AAV as a gene carrier into the inner ear, team has used a form of the virus which was wrapped in protective bubbles which were called exosomes.

It is an approach which is recently developed by means of study co-investigators Casey Maguire, HMS assistant professor of neurology at the Mass General and Xandra Breakfield, HMS professor of neurology at Mass General.

Maguire and his colleagues are grewing regular AAV virus inside the cells. These cells are naturally bud off exosomes – tiny bubbles which are made of cell membranes which are carrying the virus inside them.

Membrane which is wrapping around the virus is coated with the proteins which bind to the cell receptors.

This according to Maguire may be the reason why the bubble wrapped form of AAV or exo-AAV is binding more easily to the surface of hair cells and is penetrating them more efficiently.

Maguire who is also a co-senior author says, “Unlike current approaches in the field, we didn’t change or directly modify the virus.

Instead, we gave it a vehicle to travel in, making it better capable of navigating the terrain inside the inner ear and accessing previously resistant cells.”

Gene Entering the Hair Cells:

In the lab dish experiments, exo-AAV has successfully penetrated about 50-60 percent of the hair cells. By contrast, AAV alone has reached a mere 20 percent of the hair cells.

For testing the approach in living animals, researchers worked with mice which were born without a gene critical for the hair cell function. Such animals normally cannot hear even the loudest sounds and exhibits poor balance.

Researchers Bence Gyorgy and Cyrille Sage who were the first authors of the study have injected exo-AAV which were pre-loaded with the missing gene into the inner ears of mouse pups shortly after the birth.

Post treatment tests are also revealing that the gene even entered between 30 to 70 percent of the hair cells while reaching both of the inner and outer hair cells.

Month after the treatment, nine of 12 mice were having some level of hearing restored and could be startled by a loud clap.

Four of them could hear sounds of the 70 to 80 decibel intensity which were roughly equivalent to the conversation in a loud restaurant.

As hair cells are critical for the sense of balance mice with the damaged or missing hair cells are showing balance abnormalities.

Treated mice were having notably improved balance as compared to untreated counterparts. They are showing far lesser head tossing or running in circles both the markers of instability or disorientation.

Team is now planning for improving their gene-delivery technique over the attempt to reach an even greater proportion of hair cells.

Scientists will be testing the approach in other forms of deafness which include conditions which is causing both deafness and blindness.

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