Research quest aims to cure hearing loss at its root

By David Tenenbaum

The ultimate cause of hearing loss is usually found in the tiny hair cells that play the crucial role of converting sound waves into nerve impulses for delivery to the brain.

“Whether hearing loss is related to age, noise, or many hereditary causes, it’s the hair cell that is the Achilles heel,” says Samuel Gubbels, a surgeon-scientist at the Waisman Center at the University of Wisconsin–Madison. “When enough hair cells die, hearing is lost.”

And even though many people with severe hearing impairments can be helped with cochlear implants — electronic devices that bypass the hair cells — the ultimate treatment for 80 percent of patients with hearing loss could be to replace the hair cells.

And that is the quest of Gubbels, who is also an assistant professor of surgery at the UW School of Medicine and Public Health. Gubbels is exploring how hair cells can develop from stem cells, either in the body or the lab.

Gubbels performs the surgery to place cochlear implants and says they “are a blessing for people who have hearing loss, and I am lucky to be able to help people by implanting them. The bar for regenerative treatment is high because cochlear implants work so well.”

But cochlear implants are expensive, require surgery, and lead to a lifetime dependence on technology. Much better — but much more difficult — would be a way to replace dead hair cells.

Some scientists are exploring whether gene therapy can prolong the life of hair cells, but Gubbels is interested in regenerating them from embryonic or adult stem cells. Stem cells are early-stage cells that can divide into multiple cell types.

One approach would be to convert embryonic or adult stem cells into hair cells and then transplant them to the inner ear. But even though scientists have learned to force stem cells to develop into nerve cells, Gubbels says that milestone could be years away for hair cells.

Hair cells may actually be too specialized for transplant, Gubbels says, since nobody yet knows how to get them to take root where they are needed. “In animal experiments, they floated around in the inner ear instead of homing in on their normal location in the cochlea,” Gubbels says.

And that shifts attention to inner ear progenitor cells, a type of stem cell that can divide into hair cells and may live in the ear. Although these stem cells exist in a mouse ear for some weeks after birth, it’s not clear if adult humans have them. “If they do, and if we can figure out what triggers them to make new hair cells when needed, that might be viable approach,” says Gubbels. “They have the advantage of being where they are needed. I think this may be the most promising approach to hair cell regeneration.”

Gubbels sees multiple advantages in having a clinical practice at a major research institution that has been the site of numerous stem cell breakthroughs. “The Waisman Center and UW–Madison are fertile environments for basic science research. From my office at Waisman, world experts in stem cells are right around the corner.”

Even before the hurdles confronting stem cell therapy fall, understanding why good hair cells go bad could have a fringe benefit, Gubbels says. “If we identify why the hair cells start this process of irretrievable loss, we might find a way to prevent it.”

Hearing allows us to communicate and enjoy nature and art based on faint airborne vibrations, says Gubbels, an avid listener to many types of music. “I just had a patient with two new cochlear implants; she was so grateful that she could distinguish the honks of individual geese as they flew overhead. That makes me realize: We often take our senses for granted, and it gives me a great appreciation for the importance of restoring hearing if we can.”

Although Gubbels says the first clinical trials of stem cells in hearing loss could be as much as a decade in the future, “The holy Grail is hair cell regeneration,” he says. “Great progress has been made. We are going to get there; it’s mainly a question of when.”