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Credit: Pixabay.

Scientists regrow hair cells in mice, suggesting hearing loss is reversible after all

Credit: Pixabay.

Credit: Pixabay.

Hearing loss affects millions of people worldwide — a common health problem caused by noise, aging, disease, and heredity. Once a person loses part or all of their hearing, they cannot restore it. But is hearing loss really permanent? Not so fast, says a new study, which found that activating a certain signaling pathway caused mice to regrow hair cells.

Approximately one in three people between the ages of 65 and 74 has hearing loss, and nearly half of those older than 75 have difficulty hearing.  The most common type is sensorineural hearing loss caused by the degradation and loss of sensory hair cells in the cochlea (the auditory part of the inner ear).

Hair cells are the sensory receptors for both the auditory system and the vestibular system in our ears — and the ears of all vertebrates. They play a big part in both our hearing and our balance, transforming the sound vibrations in the cochlea into electrical signals which are fed up to auditory nerves and sent up to the brain.

If you’re a bird or frog, then you are able to regenerate hair cells. Unfortunately for humans, and all other mammals, we don’t have this ability.

“We’re the only vertebrates that can’t do it,” said Jingyuan Zhang, a researcher at the biology department at the University of Rochester, and co-author of the new study published in the European Journal of Neuroscience.

Zhang and colleagues wanted to find out whether they could treat the mammalian body into growing hearing cells, just like all other non-mammals can. They zoomed in on a group of epidermal growth factor (EGF) receptors that are known to be responsible for activating support cells in the auditory organs of birds. Once these cells are activated, they foster the generation of new sensory hair cells.

Mice, and likely all other mammals, express EGF receptors throughout their lives but are, nevertheless, unable to regenerate hair cells. The researchers at the University of Rochester have a hunch that during mammalian evolution, the expression of intracellular regulators of EGF receptors changed somehow, altering the signaling pathway. What if they could switch this pathway? That’s the million dollar question.

The team tested their theory by targeting a specific receptor called ERBB2 in cochlear support cells. In experiments, researchers used different methods to target the receptor, including a virus, drugs originally developed to stimulate stem cell activity but which are also known to activate ERBB2 signaling, and genetic modification of the mice themselves.

Activating the ERBB2 pathways unleashed a cascade of cellular events which eventually led to the proliferation of cochlear support cells, triggering neighboring stem cells to develop into new sensory hair cells.

“This research demonstrates a signaling pathway that can be activated by different methods and could represent a new approach to cochlear regeneration and, ultimately, restoration of hearing,” said says lead author Patricia White, research associate professor in the University of Rochester Medical Center (URMC) Del Monte Institute for Neuroscience.

Repairing hearing is a complex problem. Not only do hair cells require regeneration, but they also have to connect properly to the necessary network of neurons. But the findings are definitely promising, suggesting that sometime in the future, growing old may not necessarily mean you’ll have bad hearing anymore.

 

New gene delivery therapy restores partial hearing, balance in deaf mice

Using an innovative genetic editing technique, researchers have managed to partially restore both heating and balance in mice born with a condition that affects both.

Most rats exhibited improvements in both hearing and balance. Image credits: Rama / Wiki Commons

Hair cells are the sensory receptors of both the auditory system and the vestibular system in our ears — and the ears of all vertebrates. They play a big part in both our hearing and our balance, transforming the sound vibrations in the cochlea into electrical signals which are fed up to auditory nerves and sent up to the brain. The problem with them is that they’re notoriously hard to treat, and despite a number of different approaches, success has been very limited. Now, a team from Harvard Medical School (HMS) and the Massachusetts General Hospital might have found something that works.

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They used the common adeno-associated virus (AAV) as a genetic delivery service — but the trick is that they wrapped it up in protective bubbles called exosomes, an approach recently developed by study co-investigators Casey Maguire. Scientists have used AAV for genetic delivery before, but hair cells proved very difficult to penetrate, and this is where the exosomes kick in.

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

The technique involves growing the virus inside the bubbles. For some reason, the bubbles tend to bind better to the targeted area. This approach is quite novel; generally, scientists tend to modify the virus itself whereas here, researchers added external protective layers. AAV alone penetrated only 20% of hair cells, with the exosomes, it penetrated 50 to 60 percent of hair cells

“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,” said Maguire, who is also co-senior author on the study.

They tested the treatment on mice born with severe hair cell affections. The mice were unable to hear even the loudest of sounds and had visible balance problems. A month after treatment, 9 out of the 12 mice had at least some hearing restored and were startled by a loud clap, a standard behavioral test for hearing. Four of them could hear sounds of 70-80 decibels, the (rough) equivalent of a loud conversation. All mice exhibited improvements in balance.

This is a very big deal considering that 30 million Americans suffer from hearing loss and every 1 in 1,000 babies is born with some kind of hearing impairment.

Journal Reference: Bence György et al. Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV. DOI: http://dx.doi.org/10.1016/j.ymthe.2016.12.010. An accompanying commentary to the study appears in the same issue.