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Science

New Compound Regenerates Auditory Hair Cells – Partially Restores Hearing in Mice

inner ear )oleg begizov )Sometimes a drug developed to treat one disease or disorder is found to be efficacious in treating another. Such is the case with a new compound called LY-411575 which was originally developed to treat symptoms accompanying Alzheimer’s progression.

In studies of the drug, medical experts discovered that it had the remarkable ability to stimulate new growth of the tiny, super-sensitive hair cells that reside in the inner ear. Without these cells, the brain cannot adequately process and interpret sounds.

Hearing generally is made possible by a small, spiralled organ in the inner ear called the cochlea. It is the cochlea that houses the hair cells which turn variations in sound (air pressure) waves into the electro-neurological signals that the brain interprets as sound.

Such hair cells can be damaged by exposure to very loud noises and diseases (e.g., viruses). Normally, once destroyed, the cells cannot be repaired or restored.

However, the hair cells have neighboring cells called supporting cells which have the potential to become auditory hair cells but are blocked from doing so by an inhibitory, cellular signaling pathway referred to as the Notch signalling pathway.

In a study of “deafened mice”, Albert Edge and colleagues at the Harvard Medical School, Cambridge, Mass., used the new compound LY-411575 to target (i.e., block) these Notch signals by applying the compound directly to the inner ears (the cochleae) of the mice. Using a color-coding gene technique that tracks new cell growth, the researchers found a 30% increase in new hair cell growth and demonstrated that the mice were then (after several days) able to detect low frequency sound waves, such as those made by a passing automobile or the thud of a box dropping on the floor.

As a general rule, the researchers found that the frequency region of hearing recovery corresponded to the area of hair cell replacement.

“It is possible to regenerate hair cells, and that’s something that had not been possible before,” says Edge, in a recent Sci Am interview

Cochlea crosssection
cross section of the cochlea

Despite this initial success, the compound is far from being ready for trials on humans; unknown side-effects are always a problem with new experimental drugs. At its current stage of development, LY-411575 is not medically or commercially ready to replace cochlear implants — the current and still somewhat controversial (within the deaf community) treatment for hearing loss.

At present, more refinement and research is needed. There may be other inhibitory signals at work and this may mean developing newer drugs to counteract these signals.

Much about these hair cells and their neighboring cells (and their biochemical signals) is unknown. For example, it is still not understood why mammals are unable to regenerate auditory hair cells. However, It seems likely that hair cells are derived from the “trans-differentiation” of the supporting cells, which also play a critical role in the ability to interpret qualities of sound.

But this newest research promises a viable path forward and (apparently) an effective means of restoring some percentage of damaged hair cells — and that is a real success story.

Results of the research were published January 9, 2013 in the journal Neuron.

Some source material for this post came from the Sci Am article  Hear-Raising: Compound Regenerates Auditory Hair Cells, Offering a Possible Treatment for Deafness

Top Image: (inner ear) oleg_begizov via shutterstock.com

Diagram: (inner ear) Cochlea-crosssection.png: Original uploader was Oarih at en.wikipedia; derivative work: Fred the Oyster




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