Deafened mice enabled to hear again by drug

Sound sensing cells in the ears of mice could be regrown with the help of a compound found by researchers from Harvard Medical School and Massachusetts Eye and Ear Infirmary.
The team led by Dr. Albert Edge lays out their findings in the Jan. 9 issue of the journal Neuron.

The method works by blocking a key protein with a drug, in order to allow sound-sensing "hair cells" damaged by loud noises to regrow. This is a breakthrough, since mammals cannot regenerate these cells, different to birds and fish which have this capability, and many methods tried until now had failed. The team around Dr. Edge had the thesis that a cellular pathway that controls hair cells' fate might be manipulated to regenerate the cells, since their previous research on hair cells revealed that inhibition of the pathway could cell differentiation.

To facilitate this effect, the researchers tested several gamma-secretase inhibitors to find the one with the strongest regenerative effect on inner ear stem cells. They then tested that drug on adult mice that had been deafened after 2 hours in an extremely loud sound chamber. The drug prompted supporting cells in the inner ear to become hair cells, and the treated mice regained some hearing.

"We show that hair cells can be regenerated from the surrounding cells in the cochlea. These cells, called supporting cells, transdifferentiate into hair cells after inhibition of the Notch signaling pathway, and the new hair cell generation results in a recovery of hearing in the region of the cochlea where the new hair cells appear," says Dr. Albert Edge, stem cell biologist at the Massachusetts Eye and Ear Infirmary in Boston.

The results suggest that the therapy might be a possible future treatment for acute noise-induced deafness in humans. "The significance of this study is that hearing loss is a huge problem affecting 250 million worldwide," says Dr. Edge.

But the word "acute" needs to be emphasized, at least for now, on top of the completely open question if the method works at all on cells in the human ear. Since the drug was given just one day after the mice were deafened, it is not clear how well, if at all, the treatment would work if it were applied after a longer delay.

Study: Kunio Mizutari et al., Notch Inhibition Induces Cochlear Hair Cell Regeneration and Recovery of Hearing after Acoustic Trauma, Neuron, 2013, DOI: 10.1016/j.neuron.2012.10.032