By David H. Kirkwood
BOSTON—When scientists finally discover a cure for sensorineural hearing loss, the key that unlocks the door for them will probably be some mechanism to stimulate the regeneration of sensory hair cells in the human cochlea.
The toll that age, noise, ototoxic medicines, and infections take on these hair cells is the most common cause of hearing loss in humans. Thus, spurring the growth of new hair cells to replace those destroyed over a lifetime of wear and tear has long been the Holy Grail sought by researchers in this area.
In some species of birds, amphibians, and fish, when hair cells die, new ones arise spontaneously to take their place and maintain these creatures’ hearing. However, in man and other mammals, when hair cells die, new ones do not take over the job, and so the resulting hearing loss is irreversible. That’s why for decades scientists have been searching for some mechanism that will make the human auditory system work more like that of birds.
ARTICLE IN NEURON REPORTS BREAKTHROUGH
Recently, researchers from Massachusetts Eye and Ear Infirmary, Harvard Medical School, and Keio University School of Medicine in Japan took a major stride forward in this quest. Writing in the January 10 issue of the journal Neuron the scientists demonstrated that they had achieved something unprecedented: They were able to stimulate resident cells to become new hair cells in an adult mouse ear, resulting in partial recovery of hearing in ears damaged by noise trauma.
This is the first demonstration of hair cell regeneration in an adult mammal. The finding holds great potential for treatments that may someday reverse deafness in humans.
In their experiment, the researchers applied a drug to the cochlea of deaf mice. The drug they used had been shown to inhibit an enzyme called gamma-secretase. When applied to the cochlea, the drug inhibited a signal generated by a protein called Notch on the surface of cells that surround hair cells.
Scientists had previously learned that Notch signaling caused supporting cells, a type of stem cells naturally found in the ear, not to develop into hair cells. The team from Harvard, and Mass Eye and Ear, and Keio wanted to find out if turning off the Notch signal would allow hair cells to develop in the mice used in their study.
That is precisely what did happen. After being treated with the drug, supporting cells turned into new hair cells. Replacing the damaged hair cells with new ones improved hearing in the mice, and the improved hearing could be traced to the areas in which supporting cells had become new hair cells.
In an interview with the press office at Massachusetts Eye and Ear, Albert Edge, PhD, the senior author, said, “We’re excited about these results because they are a step forward in the biology of regeneration and prove that mammalian hair cells have the capacity to regenerate.” He added, “With more research, we think that regeneration of hair cells opens the door to potential therapeutic applications in deafness.”