A drug that restores hearing in deaf mice

Advances in regenerative medicine are coming in fast and furious these days, and a remarkable new breakthrough can be added to the list. Scientists at Massachusetts Eye and Ear and Harvard Medical School have restored partial hearing in mice suffering from sensorineural hearing loss — a condition that happens after prolonged exposure to noise. Given the rise of an aging population — not to mention a preponderance of people who blast their ears with portable MP3 players — it's an important bit of scientific insight that could someday help millions of people get their hearing back.

To learn more about this important breakthrough, we contacted lead researcher Dr. Albert Edge, whose study appears in the January 10 issue of Neuron.


Edge agreed that sensorineural hearing loss is a growing concern.

"The National Institute of Deafness and Communications Disorders of the NIH estimates that approximately 15 percent of Americans between the ages of 20 and 69 have hearing loss due to exposure to loud sounds or noise at work or in leisure activities," he told io9. "So this is a very serious problem with little that can be done to treat it."

No doubt, it's a problem that currently affects 250 million people worldwide.

Edge says that hearing aids can help, but his team is hoping to develop a treatment that goes all the way — one that can actually replace the lost cells.


An irreversible problem?

Indeed, it's the loss of sensory hair cells in the cochlea that causes a gradual decline in hearing quality — a condition that comes about after excessive and long-term exposure to noise, as well as aging, toxins, infections, and even some antibiotics and anti-cancer drugs. Without these hairs, the hearing pathway is blocked, and signals cannot be received in the auditory cortex of the brain.


Unlike birds and fish, mammals cannot regenerate auditory hair cells once they start to degrade — a condition that makes it harder to hear over time, and what also causes a persistent ringing in the ears (what's known as tinnitus). It was this apparent problem of irreversibility that Edge and his team confronted.

"There aren't currently any treatments and few experimental approaches," he told us. It was for this reason that they tried something a bit more radical — a drug treatment that could target the endogenous cells left in the cochlea.



And this is precisely what they managed to achieve.


Specifically, the researchers demonstrated for the first time that hair cells can in fact be regenerated in an adult mammalian ear by using a drug, codenamed LY411575, to coax nearby ear cells to transform into new hair cells. It was a technique that ultimately resulted in the partial recovery of hearing in mice who experienced ear damage caused by noise trauma (yes, the researchers deafened the mice with loud noise).

For the experiment, Edge administered the drug directly into the cochlear region of the deaf mice — a highly specialized drug selected for its ability to spawn hair cells when added to stem cells taken from the ear.


Then, after the inhibition of a protein called Notch (which is on the surface of cells that surround hair cells), the resident cells were converted into new, functional hair cells. Notch has previously been shown to prevent stem cells in the cochlea from transforming — a problem that the researchers were able to overcome.

In fact, the new hair cells created a measurable improvement in the hearing of the mice after just three months — changes that could be traced to the presence of newly generated hair cells (the scientists used a green fluorescent protein to isolate the new hair cells). And the improvements were measured over a wide range of frequencies.


"This is a new way of inducing hair cell replacement by driving remaining cochlear cells to become new hair cells," said Edge.

Moving forward, Edge told io9 that he hopes to test additional drugs and look at other forms of hearing loss. Moreover, because the therapy improved hearing in mammals, the regeneration of hair cells could introduce opportunities into potential therapeutic applications in treating sensorimotor deafness in humans.


The entire study can be found at Neuron. Also accessible here.

Image: CreativeNature.nl/Shutterstock.


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